BioPAX pathway converted from "S Phase" in the Reactome database.S PhaseThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Synthesis of DNAThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>DNA replication initiationThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>LEFT-TO-RIGHT2.7.7.6The primase component of DNA polymerase:primase synthesizes a 6-10 nucleotide RNA primer at the originThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Converted from EntitySet in ReactomeNTPReactome DB_ID: 30595ATPAdenosine 5'-triphosphateATP(4-)Reactome DB_ID: 29358nucleoplasmGENE ONTOLOGYGO:0005654ATP(4-) [ChEBI:30616]ATP(4-)ATPatpAdenosine 5'-triphosphateChEBICHEBI:30616Reactome Database ID Release 7529358Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29358ReactomeR-ALL-293583Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29358.3Reactomehttp://www.reactome.orgCOMPOUNDC00002additional informationMIMI:0361CTPcytidine 5'-triphosphateCytidine triphosphateReactome DB_ID: 29470CTP [ChEBI:17677]CTPcytidine 5'-triphosphateCytidine triphosphateChEBICHEBI:17677Reactome Database ID Release 7529470Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29470ReactomeR-ALL-294702Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29470.2COMPOUNDC00063GTPGuanosine 5'-triphosphateReactome DB_ID: 113571GTP [ChEBI:15996]GTPGuanosine 5'-triphosphateChEBICHEBI:15996Reactome Database ID Release 75113571Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113571ReactomeR-ALL-1135712Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113571.2COMPOUNDC00044UTPuridine 5'-triphosphateUridine triphosphateReactome DB_ID: 113562UTP [ChEBI:15713]UTPuridine 5'-triphosphateUridine triphosphateChEBICHEBI:15713Reactome Database ID Release 75113562Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113562ReactomeR-ALL-1135622Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113562.2COMPOUNDC00075Reactome Database ID Release 7530595Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=30595ReactomeR-ALL-305951Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-30595.1COMPOUNDC00699DNA polymerase alpha:primase:DNA polymerase alpha:origin complexReactome DB_ID: 10727260DNA polymerase alpha:primaseReactome DB_ID: 10727227POL12POLA2P38121Reactome DB_ID: 10727213UniProt:P38121POL12Saccharomyces cerevisiaeNCBI Taxonomy4932UniProtP381211EQUAL598EQUALReactome Database ID Release 7510727213Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727213ReactomeR-SCE-684931Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68493.11POL1POLA1P13382Reactome DB_ID: 10727208UniProt:P13382POL1UniProtP133821EQUAL1462EQUALReactome Database ID Release 7510727208Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727208ReactomeR-SCE-684871Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68487.11PRIM1:PRIM2Reactome DB_ID: 10727225PRI2PRIM2P20457Reactome DB_ID: 10727223UniProt:P20457PRI2UniProtP204571EQUAL509EQUALReactome Database ID Release 7510727223Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727223ReactomeR-SCE-684951Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68495.11PRI1PRIM1P10363Reactome DB_ID: 10727218UniProt:P10363PRI1UniProtP103631EQUAL420EQUALReactome Database ID Release 7510727218Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727218ReactomeR-SCE-684971Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68497.11Reactome Database ID Release 7510727225Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727225ReactomeR-SCE-96688121Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-9668812.11Reactome Database ID Release 7510727227Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727227ReactomeR-SCE-685071Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68507.11DNA polymerase epsilon:origin complexReactome DB_ID: 10727258DNA polymerase epsilonReactome DB_ID: 10727256Converted from EntitySet in ReactomeHomologues of POLE4Reactome DB_ID: 10727254DPB3POLE4P27344Reactome DB_ID: 10727247UniProt:P27344DPB3UniProtP273442EQUAL117EQUALReactome Database ID Release 7510727247Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727247ReactomeR-SCE-88666841Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-8866684.1DLS1POLE4P40366Reactome DB_ID: 10727252UniProt:P40366DLS1UniProtP403662EQUAL117EQUALReactome Database ID Release 7510727252Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727252ReactomeR-SCE-8866684-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-8866684-2.1Reactome Database ID Release 7510727254Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727254ReactomeR-SCE-8866684-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-8866684-3.11POL2POLEP21951Reactome DB_ID: 10727232UniProt:P21951POL2UniProtP219511EQUAL2286EQUALReactome Database ID Release 7510727232Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727232ReactomeR-SCE-684731Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68473.11DPB2POLE2P24482Reactome DB_ID: 10727237UniProt:P24482DPB2UniProtP244821EQUAL527EQUALReactome Database ID Release 7510727237Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727237ReactomeR-SCE-684821Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68482.11DPB4POLE3Q04603Reactome DB_ID: 10727242UniProt:Q04603DPB4UniProtQ046032EQUAL147EQUALReactome Database ID Release 7510727242Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727242ReactomeR-SCE-88666851Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-8866685.11Reactome Database ID Release 7510727256Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727256ReactomeR-SCE-684831Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68483.11ARSorigin of replicationoriginautonomously replicating sequenceReactome DB_ID: 68419Reactome Database ID Release 7568419Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68419ReactomeR-ALL-684192Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-68419.2ChEBI611201Reactome Database ID Release 7510727258Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727258ReactomeR-SCE-684851Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68485.11Reactome Database ID Release 7510727260Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727260ReactomeR-SCE-685101Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68510.1RNA primer:origin duplex:DNA polymerase alpha:primase complexReactome DB_ID: 10727262RNA primerReactome DB_ID: 68422Reactome Database ID Release 7568422Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68422ReactomeR-ALL-684223Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-68422.3ChEBI33697111Reactome Database ID Release 7510727262Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727262ReactomeR-SCE-684231Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68423.1ACTIVATIONactiveUnit: #Complex2GENE ONTOLOGYGO:0003899gene ontology term for cellular functionMIMI:0355Same Catalyst ActivityReactome Database ID Release 7510727263Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727263Reactome Database ID Release 7510727265Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727265ReactomeR-SCE-689131Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68913.1At the beginning of this reaction, 1 molecule of 'DNA polymerase alpha:primase:DNA polymerase alpha:origin complex', and 1 molecule of 'NTP' are present. At the end of this reaction, 1 molecule of 'DNA polymerase epsilon', and 1 molecule of 'RNA primer:origin duplex:DNA polymerase alpha:primase complex' are present.<br><br> This reaction takes place in the 'nucleus' and is mediated by the 'DNA-directed RNA polymerase activity' of 'DNA polymerase alpha:primase'.<br>6693436Pubmed1984DNA primase from KB cells. Characterization of a primase activity tightly associated with immunoaffinity-purified DNA polymerase-alpha.Wang, TSHu, SZKorn, DJ Biol Chem 259:1854-65inferred from electronic annotationEVIDENCE CODEECO:0000203LEFT-TO-RIGHT2.7.7.7The polymerase component of DNA polymerase alpha:primase synthesizes a 20-nucleotide primer at the originThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>dATP2'-deoxyadenosine 5'-triphosphateDeoxyadenosine 5'-triphosphateDeoxyadenosine triphosphateReactome DB_ID: 29604dATP [ChEBI:16284]dATP2'-deoxyadenosine 5'-triphosphateDeoxyadenosine 5'-triphosphateDeoxyadenosine triphosphateChEBICHEBI:16284Reactome Database ID Release 7529604Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29604ReactomeR-ALL-296042Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29604.2COMPOUNDC00131dCTPdeoxycytidine 5'-triphosphateDeoxycytidine triphosphate2'-Deoxycytidine 5'-triphosphateReactome DB_ID: 30185dCTP [ChEBI:16311]dCTPdeoxycytidine 5'-triphosphateDeoxycytidine triphosphate2'-Deoxycytidine 5'-triphosphateChEBICHEBI:16311Reactome Database ID Release 7530185Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=30185ReactomeR-ALL-301852Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-30185.2COMPOUNDC00458dGTP2'-deoxyguanosine 5'-triphosphateDeoxyguanosine 5'-triphosphateDeoxyguanosine triphosphateReactome DB_ID: 29892dGTP [ChEBI:16497]dGTP2'-deoxyguanosine 5'-triphosphateDeoxyguanosine 5'-triphosphateDeoxyguanosine triphosphateChEBICHEBI:16497Reactome Database ID Release 7529892Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29892ReactomeR-ALL-298922Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29892.2COMPOUNDC00286TTPdTTPDeoxythymidine triphosphateDeoxythymidine 5'-triphosphateReactome DB_ID: 30187dTTP [ChEBI:18077]dTTPDeoxythymidine triphosphateDeoxythymidine 5'-triphosphateTTPChEBICHEBI:18077Reactome Database ID Release 7530187Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=30187ReactomeR-ALL-301872Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-30187.2COMPOUNDC00459RNA primer-DNA primer:origin duplexReactome DB_ID: 107273871DNA primerReactome DB_ID: 68424Reactome Database ID Release 7568424Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68424ReactomeR-ALL-684242Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-68424.2ChEBI611201Reactome Database ID Release 7510727387Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727387ReactomeR-SCE-684251Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68425.1ACTIVATIONGENE ONTOLOGYGO:0003887Reactome Database ID Release 7510727388Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727388Reactome Database ID Release 7510727390Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727390ReactomeR-SCE-689501Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68950.1At the beginning of this reaction, 1 molecule of 'dTTP', 1 molecule of 'dGTP', 1 molecule of 'dATP', 1 molecule of 'RNA primer:origin duplex:DNA polymerase alpha:primase complex', and 1 molecule of 'dCTP' are present. At the end of this reaction, 1 molecule of 'RNA primer-DNA primer:origin duplex' is present.<br><br> This reaction takes place in the 'nucleus' and is mediated by the 'DNA-directed DNA polymerase activity' of 'DNA polymerase alpha:primase'.<br>6094569Pubmed1984Purification of a DNA polymerase-DNA primase complex from calf thymus glandsChang, L MRafter, EAugl, CBollum, F JJ. Biol. Chem. 259:14679-87Reactome Database ID Release 7510753051Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10753051ReactomeR-SCE-689521Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68952.1GENE ONTOLOGYGO:0006270gene ontology term for cellular processMIMI:0359DNA polymerases are not capable of de novo DNA synthesis and require synthesis of a primer, usually by a DNA-dependent RNA polymerase (primase) to begin DNA synthesis. In eukaryotic cells, the primer is synthesized by DNA polymerase alpha:primase. First, the DNA primase portion of this complex synthesizes approximately 6-10 nucleotides of RNA primer and then the DNA polymerase portion synthesizes an additional 20 nucleotides of DNA (Frick & Richardson 2002; Wang et al 1984).11395402Pubmed2002DNA primases.Frick, DNRichardson, CCAnnu Rev Biochem 70:39-80Switching of origins to a post-replicative stateThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Orc1 removal from chromatinThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>LEFT-TO-RIGHTUbiquitinated Orc1 enters the cytosolThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>P54784phospho-ORC1PolyUb,p-S,T-ORC1Reactome DB_ID: 10727381UniProt:P54784ORC1UniProtP54784O-phospho-L-serineMODMOD:00046O-phospho-L-threonineMODMOD:00047ubiquitinylated lysineMODMOD:011481EQUAL861EQUALReactome Database ID Release 7510727381Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727381ReactomeR-SCE-90321891Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-9032189.1P54784phospho-ORC1PolyUb,p-S,T-ORC1Reactome DB_ID: 10727383cytosolGENE ONTOLOGYGO:00058291EQUAL861EQUALReactome Database ID Release 7510727383Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727383ReactomeR-SCE-90321951Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-9032195.1Reactome Database ID Release 7510727385Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727385ReactomeR-SCE-689471Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68947.1Ubiquitinated ORC1 translocates to the cytosol (Li and DePamphilis 2002). 11739726Pubmed2001Mammalian Orc1 protein is selectively released from chromatin and ubiquitinated during the S-to-M transition in the cell division cycle.Li, CJDePamphilis, MLMol Cell Biol 22:105-16Reactome Database ID Release 7510753067Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10753067ReactomeR-SCE-689491Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68949.1Mammalian Orc1 protein is phosphorylated and selectively released from chromatin and ubiquitinated during the S-to-M transition in the cell division cycle.11931757Pubmed2002Human origin recognition complex large subunit is degraded by ubiquitin-mediated proteolysis after initiation of DNA replication.Mendez, JZou-Yang, XHKim, SYHidaka, MTansey, WPStillman, BMol Cell 9:481-911110244Pubmed1975Forearm blood flow during body temperature transients produced by leg exercise.Wenger, CBRoberts, MFStolwijk, JANadel, ERJ Appl Physiol 38:58-6311809796Pubmed2002Identification of a binding region for human origin recognition complex proteins 1 and 2 that coincides with an origin of DNA replication.Ladenburger, EMKeller, CKnippers, RMol Cell Biol 22:1036-48CDK-mediated phosphorylation and removal of Cdc6This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>LEFT-TO-RIGHT2.7.11.22Cdc6 protein is phosphorylated by CDKThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>CDC6CDC6P09119Reactome DB_ID: 10727201UniProt:P09119CDC6UniProtP091191EQUAL560EQUALReactome Database ID Release 7510727201Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727201ReactomeR-SCE-685421Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68542.1p-CDC6phospho-CDC6P09119Reactome DB_ID: 10727400phosphorylated residueMODMOD:006961EQUAL560EQUALReactome Database ID Release 7510727400Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727400ReactomeR-SCE-56613171Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-5661317.1ADPAdenosine 5'-diphosphateADP(3-)Reactome DB_ID: 113582ADP(3-) [ChEBI:456216]ADP(3-)ADP5&apos;-O-[(phosphonatooxy)phosphinato]adenosineADP trianionChEBICHEBI:456216Reactome Database ID Release 75113582Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113582ReactomeR-ALL-1135823Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113582.3COMPOUNDC00008ACTIVATIONCyclin E:p-T160-CDK2Reactome DB_ID: 10727439Converted from EntitySet in ReactomeCyclin EReactome DB_ID: 10727434Converted from EntitySet in ReactomeHomologues of CCNE1Reactome DB_ID: 10727422CLB1CCNE1P24868Reactome DB_ID: 10727405UniProt:P24868CLB1UniProtP248681EQUAL410EQUALReactome Database ID Release 7510727405Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727405ReactomeR-SCE-683631Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68363.1CLB2CCNE1P24869Reactome DB_ID: 10727410UniProt:P24869CLB2UniProtP248691EQUAL410EQUALReactome Database ID Release 7510727410Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727410ReactomeR-SCE-68363-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68363-2.1CLB5CCNE1P30283Reactome DB_ID: 10727415UniProt:P30283CLB5UniProtP302831EQUAL410EQUALReactome Database ID Release 7510727415Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727415ReactomeR-SCE-68363-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68363-3.1CLB6CCNE1P32943Reactome DB_ID: 10727420UniProt:P32943CLB6UniProtP329431EQUAL410EQUALReactome Database ID Release 7510727420Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727420ReactomeR-SCE-68363-41Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68363-4.1Reactome Database ID Release 7510727422Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727422ReactomeR-SCE-68363-51Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68363-5.1Converted from EntitySet in ReactomeHomologues of CCNE2Reactome DB_ID: 10727432CLB1CCNE2P24868Reactome DB_ID: 107274241EQUAL404EQUALReactome Database ID Release 7510727424Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727424ReactomeR-SCE-683671Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68367.1CLB2CCNE2P24869Reactome DB_ID: 107274261EQUAL404EQUALReactome Database ID Release 7510727426Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727426ReactomeR-SCE-68367-21Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68367-2.1CLB5CCNE2P30283Reactome DB_ID: 107274281EQUAL404EQUALReactome Database ID Release 7510727428Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727428ReactomeR-SCE-68367-31Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68367-3.1CLB6CCNE2P32943Reactome DB_ID: 107274301EQUAL404EQUALReactome Database ID Release 7510727430Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727430ReactomeR-SCE-68367-41Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68367-4.1Reactome Database ID Release 7510727432Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727432ReactomeR-SCE-68367-51Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68367-5.1Reactome Database ID Release 7510727434Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727434ReactomeR-SCE-683731Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68373.11P00546phospho-CDC28p-T160-CDK2Reactome DB_ID: 10727437UniProt:P00546CDC28UniProtP00546160EQUAL1EQUAL298EQUALReactome Database ID Release 7510727437Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727437ReactomeR-SCE-1879671Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-187967.11Reactome Database ID Release 7510727439Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727439ReactomeR-SCE-1883621Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-188362.1GENE ONTOLOGYGO:0004693Reactome Database ID Release 7510727440Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727440Reactome Database ID Release 7510727442Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727442ReactomeR-SCE-690051Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-69005.1At the beginning of this reaction, 1 molecule of 'CDC6', and 1 molecule of 'ATP' are present. At the end of this reaction, 1 molecule of 'ADP', and 1 molecule of 'phosphorylated Cdc6' are present.<br><br> This reaction takes place in the 'nucleus' and is mediated by the 'kinase activity' of 'CDK'.<br>10339564Pubmed1999Multistep regulation of DNA replication by Cdk phosphorylation of HsCdc6.Jiang, WWells, NJHunter, TonyProc Natl Acad Sci U S A 96:6193-8LEFT-TO-RIGHTPhosphorylated Cdc6 is exported from the nucleusThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>p-CDC6phospho-CDC6P09119Reactome DB_ID: 107274441EQUAL560EQUALReactome Database ID Release 7510727444Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727444ReactomeR-SCE-685831Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68583.1Reactome Database ID Release 7510727446Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727446ReactomeR-SCE-690061Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-69006.1In this reaction, 1 molecule of 'phosphorylated Cdc6' is translocated from nucleoplasm to cytosol.<br><br>This movement of the molecule occurs through the 'nuclear pore'.<br>Reactome Database ID Release 7510753071Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10753071ReactomeR-SCE-690171Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-69017.1As cells enter S phase, HsCdc6p is phosphorylated by CDK promoting its export from the nucleus (see Bell and Dutta 2002). 12045100Pubmed2002DNA replication in eukaryotic cells.Bell, SPDutta, AAnnu Rev Biochem 71:333-7411046155Pubmed2000Chromatin association of human origin recognition complex, cdc6, and minichromosome maintenance proteins during the cell cycle: assembly of prereplication complexes in late mitosis.Mendez, JStillman, BMol Cell Biol 20:8602-12LEFT-TO-RIGHTRearrangement and mobilization of Mcm2-7Mcm4,6,7 trimer forms and associates with the replication forkThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>MCM2-7Reactome DB_ID: 10727335MCM4MCM4P30665Reactome DB_ID: 10727317UniProt:P30665 MCM4MCM4CDC54HCD21YPR019WYP9531.13FUNCTION Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity. Once loaded onto DNA, double hexamers can slide on dsDNA in the absence of ATPase activity. Required for S phase execution.SUBUNIT Component of the MCM2-7 complex. The complex forms a toroidal hexameric ring with the proposed subunit order MCM2-MCM6-MCM4-MCM7-MCM3-MCM5; loaded onto DNA, forms a head-head double hexamer.MISCELLANEOUS Present with 8800 molecules/cell in log phase SD medium.MISCELLANEOUS Early fractionation of eukaryotic MCM proteins yielded a variety of dimeric, trimeric and tetrameric complexes with unclear biological significance. Specifically a MCM467 subcomplex is shown to have in vitro helicase activity which is inhibited by the MCM2 subunit. The MCM2-7 hexamer is the proposed physiological active complex.SIMILARITY Belongs to the MCM family.UniProtP306652EQUAL863EQUALReactome Database ID Release 7510727317Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727317ReactomeR-SCE-685491Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68549.11MCM5MCM5P29496Reactome DB_ID: 10727321UniProt:P29496 MCM5MCM5CDC46YLR274WL9328.1FUNCTION Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity; specifically the MCM2-MCM5 association is proposed to be reversible and to mediate a open ring conformation which may facilitate DNA loading. Once loaded onto DNA, double hexamers can slide on dsDNA in the absence of ATPase activity.SUBUNIT Component of the MCM2-7 complex. The complex forms a toroidal hexameric ring with the proposed subunit order MCM2-MCM6-MCM4-MCM7-MCM3-MCM5; loaded onto DNA, forms a head-head double hexamer. Interacts with CSM1.MISCELLANEOUS Present with 10300 molecules/cell in log phase SD medium.MISCELLANEOUS Early fractionation of eukaryotic MCM proteins yielded a variety of dimeric, trimeric and tetrameric complexes with unclear biological significance. The MCM2-7 hexamer is the proposed physiological active complex.SIMILARITY Belongs to the MCM family.UniProtP294961EQUAL734EQUALReactome Database ID Release 7510727321Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727321ReactomeR-SCE-685511Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68551.11MCM7MCM7P38132Reactome DB_ID: 10727329UniProt:P38132 MCM7MCM7CDC47YBR202WYBR1441FUNCTION Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity. Once loaded onto DNA, double hexamers can slide on dsDNA in the absence of ATPase activity.SUBUNIT Component of the MCM2-7 complex. The complex forms a toroidal hexameric ring with the proposed subunit order MCM2-MCM6-MCM4-MCM7-MCM3-MCM5; loaded onto DNA, forms a head-head double hexamer. Interacts with CSM1 and MCM10.MISCELLANEOUS Present with 166 molecules/cell in log phase SD medium.MISCELLANEOUS Early fractionation of eukaryotic MCM proteins yielded a variety of dimeric, trimeric and tetrameric complexes with unclear biological significance. Specifically a MCM467 subcomplex is shown to have in vitro helicase activity which is inhibited by the MCM2 subunit. The MCM2-7 hexamer is the proposed physiological active complex.SIMILARITY Belongs to the MCM family.UniProtP381322EQUAL719EQUALReactome Database ID Release 7510727329Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727329ReactomeR-SCE-685551Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68555.11MCM3MCM3P24279Reactome DB_ID: 10727313UniProt:P24279 MCM3MCM3YEL032WSYGP-ORF23FUNCTION Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity. Once loaded onto DNA, double hexamers can slide on dsDNA in the absence of ATPase activity. Necessary for cell growth.SUBUNIT Component of the MCM2-7 complex. The complex forms a toroidal hexameric ring with the proposed subunit order MCM2-MCM6-MCM4-MCM7-MCM3-MCM5; loaded onto DNA, forms a head-head double hexamer. Interacts with CSM1.MISCELLANEOUS Present with 35100 molecules/cell in log phase SD medium.MISCELLANEOUS Early fractionation of eukaryotic MCM proteins yielded a variety of dimeric, trimeric and tetrameric complexes with unclear biological significance. The MCM2-7 hexamer is the proposed physiological active complex.SIMILARITY Belongs to the MCM family.UniProtP242792EQUAL808EQUALReactome Database ID Release 7510727313Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727313ReactomeR-SCE-685461Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68546.11MCM6MCM6P53091Reactome DB_ID: 10727325UniProt:P53091 MCM6MCM6YGL201CFUNCTION Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity. Once loaded onto DNA, double hexamers can slide on dsDNA in the absence of ATPase activity. Required for the entry in S phase and for cell division.SUBUNIT Component of the MCM2-7 complex. The complex forms a toroidal hexameric ring with the proposed subunit order MCM2-MCM6-MCM4-MCM7-MCM3-MCM5; loaded onto DNA, forms a head-head double hexamer. Interacts with MCM10.MISCELLANEOUS Present with 13400 molecules/cell in log phase SD medium.MISCELLANEOUS Early fractionation of eukaryotic MCM proteins yielded a variety of dimeric, trimeric and tetrameric complexes with unclear biological significance. Specifically a MCM467 subcomplex is shown to have in vitro helicase activity which is inhibited by the MCM2 subunit. The MCM2-7 hexamer is the proposed physiological active complex.SIMILARITY Belongs to the MCM family.UniProtP530911EQUAL821EQUALReactome Database ID Release 7510727325Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727325ReactomeR-SCE-685531Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68553.11MCM2MCM2P29469Reactome DB_ID: 10727333UniProt:P29469 MCM2MCM2YBL023CYBL0438FUNCTION Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity; specifically the MCM2-MCM5 association is proposed to be reversible and to mediate a open ring conformation which may facilitate DNA loading. Once loaded onto DNA, double hexamers can slide on dsDNA in the absence of ATPase activity. Necessary for cell growth.SUBUNIT Component of the MCM2-7 complex. The complex forms a toroidal hexameric ring with the proposed subunit order MCM2-MCM6-MCM4-MCM7-MCM3-MCM5; loaded onto DNA, forms a head-head double hexamer.MISCELLANEOUS Present with 1690 molecules/cell in log phase SD medium.MISCELLANEOUS Early fractionation of eukaryotic MCM proteins yielded a variety of dimeric, trimeric and tetrameric complexes with unclear biological significance. Specifically a MCM467 subcomplex is shown to have in vitro helicase activity which is inhibited by the MCM2 subunit. The MCM2-7 hexamer is the proposed physiological active complex.SIMILARITY Belongs to the MCM family.UniProtP294692EQUAL904EQUALReactome Database ID Release 7510727333Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727333ReactomeR-SCE-685571Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68557.11Reactome Database ID Release 7510727335Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727335ReactomeR-SCE-685581Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68558.1Mcm4,6,7 complexReactome DB_ID: 10727448111Reactome Database ID Release 7510727448Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727448ReactomeR-SCE-690181Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-69018.1Reactome Database ID Release 7510727450Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727450ReactomeR-SCE-690191Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-69019.1At the start of the elongation phase of DNA replication, the Mcm2-7 complex may re-arrange to function as the replicative helicase associated with the replication fork. In general, a replicative helicase is associated with the replication fork and unwinds DNA ahead of the polymerase. In yeast, the Mcm proteins associate with origin DNA in G1 phase and then exit the origin upon replication initiation, consistent with moving out of the origin with the replication fork. The Mcm2-7 complex is a ring-shaped hexamer. Complexes of Mcm4, Mcm6 and Mcm7 proteins from humans or S. pombe display a modest ATP-dependent helicase activity in vitro. Consistent with the hypothesis that eukaryotic Mcm complexes function as helicases, an archaeal Mcm homolog is a ring-shaped double hexamer that has a processive DNA unwinding activity. Mcm proteins may have additional functions during elongation, as uninterrupted function of all six is required for replication fork progression in budding yeast. Mcm4,6,7 helicase activity may be negatively regulated in two ways. Mcm2, Mcm4, Mcm6, and Mcm7 also form a stable complex which, however, has no helicase activity, suggesting that Mcm2 inhibits DNA unwinding by Mcm4,6,7. In addition, phosphorylation of human Mcm4,6,7 complex by CDK inhibits its helicase activity.10611290Pubmed2000The single minichromosome maintenance protein of Methanobacterium thermoautotrophicum DeltaH contains DNA helicase activity.Kelman, ZLee, JKHurwitz, JProc Natl Acad Sci U S A 96:14783-811282021Pubmed2001Initiating DNA synthesis: from recruiting to activating the MCM complex.Lei, MTye, Bik KJ Cell Sci 114:1447-549335335Pubmed1997Components and dynamics of DNA replication complexes in S. cerevisiae: redistribution of MCM proteins and Cdc45p during S phase.Aparicio, OMWeinstein, DMBell, SPCell 91:59-6910567526Pubmed2000Biochemical analysis of the intrinsic Mcm4-Mcm6-mcm7 DNA helicase activity.You, ZKomamura, YIshimi, YMol Cell Biol 19:8003-1510872463Pubmed2000MCM proteins in DNA replication.Tye, Bik KAnnu Rev Biochem 68:649-8611454864Pubmed2001Phosphorylation of Mcm4 at specific sites by cyclin-dependent kinase leads to loss of Mcm4,6,7 helicase activity.Ishimi, YKomamura-Kohno, YJ Biol Chem 276:34428-3310834843Pubmed2000Uninterrupted MCM2-7 function required for DNA replication fork progression.Labib, KTercero, JADiffley, JFScience 288:1643-710748114Pubmed2000Inhibition of Mcm4,6,7 helicase activity by phosphorylation with cyclin A/Cdk2.Ishimi, YKomamura-Kohno, YYou, ZOmori, AKitagawa, MJ Biol Chem 275:16235-419305914Pubmed1997A DNA helicase activity is associated with an MCM4, -6, and -7 protein complex.Ishimi, YJ Biol Chem 272:24508-1310677495Pubmed2000A double-hexamer archaeal minichromosome maintenance protein is an ATP-dependent DNA helicase.Chong, JPHayashi, MKSimon, MNXu, RMStillman, BProc Natl Acad Sci U S A 97:1530-510884341Pubmed2000Electron microscopic observation and single-stranded DNA binding activity of the Mcm4,6,7 complex.Sato, MGotow, TYou, ZKomamura-Kohno, YUchiyama, YYabuta, NNojima, HIshimi, YJ Mol Biol 300:421-3112364596Pubmed2002Human Mcm proteins at a replication origin during the G1 to S phase transition.Schaarschmidt, DLadenburger, EMKeller, CKnippers, RNucleic Acids Res 30:4176-85Reactome Database ID Release 7510753069Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10753069ReactomeR-SCE-690521Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-69052.1Switching of origins to a post-replicative state involves the removal of Orc1 from chromatin, CDK-mediated phosphorylation and removal of Cdc6, and the rearrangement and mobilization of Mcm2-7.DNA strand elongationThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Unwinding of DNAThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>LEFT-TO-RIGHTFormation of GINS complexThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>PSF3GINS3Q12146Reactome DB_ID: 10732884UniProt:Q12146PSF3UniProtQ121461EQUAL216EQUALReactome Database ID Release 7510732884Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10732884ReactomeR-SCE-56880461Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-5688046.1PSF1GINS1Q12488Reactome DB_ID: 10732874UniProt:Q12488PSF1UniProtQ124881EQUAL196EQUALReactome Database ID Release 7510732874Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10732874ReactomeR-SCE-1769551Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-176955.1PSF2GINS2P40359Reactome DB_ID: 10732879UniProt:P40359PSF2UniProtP403591EQUAL185EQUALReactome Database ID Release 7510732879Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10732879ReactomeR-SCE-1769751Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-176975.1SLD5GINS4Q03406Reactome DB_ID: 10732889UniProt:Q03406SLD5UniProtQ034061EQUAL223EQUALReactome Database ID Release 7510732889Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10732889ReactomeR-SCE-1769631Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-176963.1GINS complexReactome DB_ID: 107328911111Reactome Database ID Release 7510732891Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10732891ReactomeR-SCE-1769521Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-176952.1Reactome Database ID Release 7510732893Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10732893ReactomeR-SCE-1769561Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-176956.1At the beginning of this reaction, 1 molecule of 'PSF3p', 1 molecule of 'SLD5P', 1 molecule of 'PSF2p', and 1 molecule of 'PSF1p' are present. At the end of this reaction, 1 molecule of 'GINS complex' is present.<br><br> This reaction takes place in the 'nucleus'.<br>17417653Pubmed2007Structure of the human GINS complex and its assembly and functional interface in replication initiationKamada, KatsuhikoKubota, YumikoArata, ToshiakiShindo, YosukeHanaoka, FumioNat. Struct. Mol. Biol. 14:388-96Reactome Database ID Release 7510753637Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10753637ReactomeR-SCE-1769741Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-176974.1DNA Replication is regulated accurately and precisely by various protein complexes. Many members of the MCM protein family are assembled into the pre-Replication Complexes (pre-RC) at the end of M phase of the cell cycle. DNA helicase activity of some of the MCM family proteins are important for the unwinding of DNA and initiation of replication processes. This section contains four events which have been proved in different eukaryotic experimental systems to involve various proteins for this essential step during DNA Replication.15707891Pubmed2005MCM8 is an MCM2-7-related protein that functions as a DNA helicase during replication elongation and not initiationMaiorano, DCuvier, ODanis, EMechali, MCell 120:315-28Leading Strand SynthesisThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Polymerase switchingThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>LEFT-TO-RIGHTRFC binding displaces Pol AlphaThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>RFC HeteropentamerReactome DB_ID: 10727477RFC4RFC2P40339Reactome DB_ID: 10727470UniProt:P40339RFC4UniProtP403391EQUAL354EQUALReactome Database ID Release 7510727470Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727470ReactomeR-SCE-684331Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68433.11RFC2RFC4P40348Reactome DB_ID: 10727460UniProt:P40348RFC2UniProtP403481EQUAL363EQUALReactome Database ID Release 7510727460Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727460ReactomeR-SCE-684291Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68429.11RFC5RFC3P38251Reactome DB_ID: 10727465UniProt:P38251RFC5UniProtP382511EQUAL356EQUALReactome Database ID Release 7510727465Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727465ReactomeR-SCE-684311Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68431.11RFC3RFC5P38629Reactome DB_ID: 10727455UniProt:P38629RFC3UniProtP386291EQUAL340EQUALReactome Database ID Release 7510727455Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727455ReactomeR-SCE-684271Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68427.11RFC1RFC1P38630Reactome DB_ID: 10727475UniProt:P38630RFC1UniProtP386301EQUAL1148EQUALReactome Database ID Release 7510727475Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727475ReactomeR-SCE-684351Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68435.11Reactome Database ID Release 7510727477Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727477ReactomeR-SCE-684361Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68436.1RFC Heteropentamer:RNA primer-DNA primer:origin duplexReactome DB_ID: 1072747911Reactome Database ID Release 7510727479Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727479ReactomeR-SCE-684371Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68437.1Reactome Database ID Release 7510727481Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727481ReactomeR-SCE-690531Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-69053.1Once the RNA-DNA primer is synthesized, replication factor C (RFC) initiates a reaction called "polymerase switching"; pol delta, the processive enzyme, replaces pol alpha, the priming enzyme. RFC binds to the 3'-end of the RNA-DNA primer on the Primosome, to displace the pol alpha primase complex. The binding of RFC triggers the binding of the primer recognition complex (Tsurimoto and Stillman 1991, Maga et al. 2000, Mossi et al. 2000). RFC is recruited to telomeres via interaction with 5'-phosphate ends of a telomere repeat sequence (Uchiumi et al. 1996, Uchiumi et al. 1999). In budding yeast, the alternative evolutionarily conserved RFC complex in which the RFC1 subunit is substituted with the CTF18 complex (composed of CHTF18, CHTF8 and DSCC1) plays a critical role in telomere maintenance (Hiraga et al. 2006, Gao et al. 2014). The CTF18-RFC complex is also implicated in telomere maintenance in fission yeast (Khair et al. 2010). It was shown that the human CTF18-RFC complex has a redundant function with the RFC pentamer in PCNA loading and DNA replication (Bermudez et al. 2003), but its role in human telomere maintenance has not been studied. Mouse CFT18 complex is necessary for proper development of germ cells (Berkowitz et al. 2012).8954124Pubmed1996Replication factor C recognizes 5'-phosphate ends of telomeresUchiumi, FOhta, TTanuma, SBiochem. Biophys. Res. Commun. 229:310-520505337Pubmed2010Roles of the checkpoint sensor clamp Rad9-Rad1-Hus1 (911)-complex and the clamp loaders Rad17-RFC and Ctf18-RFC in Schizosaccharomyces pombe telomere maintenanceKhair, LyneChang, Ya-TingSubramanian, LakxmiRussell, PaulNakamura, Toru MCell Cycle 9:2237-4810656792Pubmed2000DNA polymerase switching: II. Replication factor C abrogates primer synthesis by DNA polymerase alpha at a critical length.Mossi, RKeller, RCFerrari, EHubscher, UJ Mol Biol 295:803-1424533124Pubmed2014The Ctf18RFC clamp loader is essential for telomere stability in telomerase-negative and mre11 mutant allelesGao, HonghaiMoss, Daniel LParke, CourtneyTatum, DanielleLustig, Arthur JPLoS ONE 9:e886331671046Pubmed1991Replication factors required for SV40 DNA replication in vitro. II. Switching of DNA polymerase alpha and delta during initiation of leading and lagging strand synthesis.Tsurimoto, TStillman, BJ Biol Chem 266:1961-810329413Pubmed1999Characterization of telomere-binding activity of replication factor C large subunit p140Uchiumi, FWatanabe, MTanuma, S iBiochem. Biophys. Res. Commun. 258:482-912930902Pubmed2003The alternative Ctf18-Dcc1-Ctf8-replication factor C complex required for sister chromatid cohesion loads proliferating cell nuclear antigen onto DNABermudez, Vladimir PManiwa, YoshimasaTappin, IngerOzato, KYokomori, KyokoHurwitz, JerardProc. Natl. Acad. Sci. U.S.A. 100:10237-4223133398Pubmed2012Disruption of CHTF18 causes defective meiotic recombination in male miceBerkowitz, Karen MSowash, Aislinn RKoenig, Lydia RUrcuyo, DawnetteKhan, FahmidaYang, FangWang, P JeremyJongens, Thomas AKaestner, Klaus HPLoS Genet. 8:e100299610656791Pubmed2000DNA polymerase switching: I. Replication factor C displaces DNA polymerase alpha prior to PCNA loading.Maga, GStucki, MSpadari, SHubscher, UJ Mol Biol 295:791-80116525505Pubmed2006The Ctf18 RFC-like complex positions yeast telomeres but does not specify their replication timeHiraga, Shin-ichiroRobertson, E DouglasDonaldson, Anne DEMBO J. 25:1505-14LEFT-TO-RIGHTLoading of PCNA - Sliding Clamp FormationThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>PCNA homotrimerReactome DB_ID: 10727488PCNAPOL30P15873Reactome DB_ID: 10727486UniProt:P15873POL30UniProtP158731EQUAL261EQUALReactome Database ID Release 7510727486Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727486ReactomeR-SCE-684391Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68439.13Reactome Database ID Release 7510727488Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727488ReactomeR-SCE-684401Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68440.1RFC Heteropentamer:RNA primer-DNA primer:origin duplex:PCNA homotrimerReactome DB_ID: 1072749011Reactome Database ID Release 7510727490Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727490ReactomeR-SCE-684711Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68471.1Reactome Database ID Release 7510727492Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727492ReactomeR-SCE-690631Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-69063.1The binding of the primer recognition complex involves the loading of the proliferating cell nuclear antigen (PCNA). Replication Factor C (RFC) transiently opens the PCNA toroid in an ATP-dependent reaction, and then allows PCNA to re-close around the double helix adjacent to the primer terminus. This leads to the formation of the "sliding clamp" (Tsurimoto et al. 1990, Mossi and Hubscher 1998). In a human telomere replication model, RFC-mediated PCNA loading increases the processivity of telomeric C-strand synthesis, but does not eliminate polymerase delta stalling on the G-rich template (Lormand et al. 2013).<br>Interaction of RTEL1 with PCNA is needed for telomere replication and maintenance of telomere integrity (Vannier et al. 2013).2165567Pubmed1990Sequential initiation of lagging and leading strand synthesis by two different polymerase complexes at the SV40 DNA replication origin.Tsurimoto, TMelendy, TStillman, BNature 346:534-99660172Pubmed1998Clamping down on clamps and clamp loaders--the eukaryotic replication factor C.Mossi, RHubscher, UEur J Biochem 254:209-16LEFT-TO-RIGHTRFC dissociates after sliding clamp formationThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>RNA primer-DNA primer:origin duplex:PCNA Reactome DB_ID: 1072749411Reactome Database ID Release 7510727494Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727494ReactomeR-SCE-684411Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68441.1Reactome Database ID Release 7510727496Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727496ReactomeR-SCE-690681Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-69068.1It is assumed that, as shown for generic DNA replication (Podust et al. 1998), the RFC complex dissociates from PCNA following sliding clamp formation at the telomere, and the DNA toroid alone tethers pol delta to the DNA.9822671Pubmed1998Replication factor C disengages from proliferating cell nuclear antigen (PCNA) upon sliding clamp formation, and PCNA itself tethers DNA polymerase delta to DNA.Podust, VNTiwari, NStephan, SJ Biol Chem 273:31992-9Reactome Database ID Release 7510753073Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10753073ReactomeR-SCE-690911Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-69091.1After the primers are synthesized, Replication Factor C binds to the 3'-end of the initiator DNA to trigger polymerase switching. The non-processive nature of pol alpha catalytic activity and the tight binding of Replication Factor C to the primer-template junction presumably lead to the turnover of the pol alpha:primase complex. After the Pol alpha-primase primase complex is displaced from the primer, the proliferating cell nuclear antigen (PCNA) binds to form a "sliding clamp" structure. Replication Factor C then dissociates, and DNA polymerase delta binds and catalyzes the processive synthesis of DNA.1670772Pubmed1991Studies on the activator 1 protein complex, an accessory factor for proliferating cell nuclear antigen-dependent DNA polymerase delta.Lee, SHKwong, ADPan, ZQHurwitz, JJ Biol Chem 266:594-6021967833Pubmed1990Functions of replication factor C and proliferating-cell nuclear antigen: functional similarity of DNA polymerase accessory proteins from human cells and bacteriophage T4.Tsurimoto, TStillman, BProc Natl Acad Sci U S A 87:1023-7Reactome Database ID Release 7510753079Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10753079ReactomeR-SCE-691091Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-69109.1The processive complex is responsible for synthesizing at least 5-10 kb of DNA in a continuous manner during leading strand synthesis. The incorporation of nucleotides by pol delta is quite accurate. However, incorporation of an incorrect nucleotide does occur occasionally. Misincorporated nucleotides are removed by the 3' to 5' exonucleolytic proofreading capability of pol delta.2175912Pubmed1991Studies on the initiation and elongation reactions in the simian virus 40 DNA replication system.Matsumoto, TEki, THurwitz, JProc Natl Acad Sci U S A 87:9712-67378348Pubmed1980Purification of deoxyribonucleic acid polymerase delta from calf thymus: partial characterization of physical properties.Lee, MYTan, CKSo, AGDowney, KMBiochemistry 19:2096-1019191022Pubmed1997DNA polymerase delta, an essential enzyme for DNA transactions.Hindges, RHubscher, UBiol Chem 378:345-62Lagging Strand SynthesisThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Processive synthesis on the lagging strandThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>LEFT-TO-RIGHTFormation of the Flap IntermediateThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Processive complex:Okazaki fragment complexReactome DB_ID: 10727515Okazaki fragmentReactome DB_ID: 68452Reactome Database ID Release 7568452Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68452ReactomeR-ALL-684522Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-68452.2ChEBI611201Processive complexReactome DB_ID: 10727513DNA Polymerase delta tetramerReactome DB_ID: 10727511POL31POLD2P46957Reactome DB_ID: 10727501UniProt:P46957POL31UniProtP469571EQUAL469EQUALReactome Database ID Release 7510727501Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727501ReactomeR-SCE-684431Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68443.11POL3POLD1P15436Reactome DB_ID: 10727509UniProt:P15436 POL3POL3CDC2TEX1YDL102WD2366FUNCTION Catalytic component of DNA polymerase delta (DNA polymerase III) which participates in chromosomal DNA replication (PubMed:2670563, PubMed:22119860, PubMed:31488849). Required during synthesis of the lagging DNA strands at the replication fork, binds at/or near replication origins and moves along DNA with the replication fork (PubMed:31488849). Participates in leading strand synthesis during replication initiation and termination (PubMed:31488849). Has 3'-5' proofreading exonuclease activity that corrects errors arising during DNA replication (PubMed:1648480).SUBUNIT DNA polymerase delta is a heterotrimer of POL3, POL32 and HYS2. Interacts with PCNA.DOMAIN The CysA-type zinc finger is required for PCNA-binding.DOMAIN The CysB motif binds 1 4Fe-4S cluster and is required for the formation of polymerase complexes.MISCELLANEOUS In eukaryotes there are five DNA polymerases: alpha, beta, gamma, delta, and epsilon which are responsible for different reactions of DNA synthesis.SIMILARITY Belongs to the DNA polymerase type-B family.UniProtP154361EQUAL1107EQUALReactome Database ID Release 7510727509Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727509ReactomeR-SCE-684491Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68449.11Ghost homologue of POLD4Reactome DB_ID: 10727505Reactome Database ID Release 7510727505Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727505ReactomeR-SCE-684471Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68447.11Ghost homologue of POLD3Reactome DB_ID: 10727503Reactome Database ID Release 7510727503Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727503ReactomeR-SCE-684451Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68445.11Reactome Database ID Release 7510727511Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727511ReactomeR-SCE-684501Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68450.111Reactome Database ID Release 7510727513Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727513ReactomeR-SCE-684511Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68451.11Reactome Database ID Release 7510727515Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727515ReactomeR-SCE-684531Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68453.1Processive complex:Okazaki fragment:FlapReactome DB_ID: 107275171FlapReactome DB_ID: 68454Reactome Database ID Release 7568454Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68454ReactomeR-ALL-684542Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-68454.2ChEBI611201Reactome Database ID Release 7510727517Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727517ReactomeR-SCE-684551Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68455.1Reactome Database ID Release 7510727519Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727519ReactomeR-SCE-691271Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-69127.1When the polymerase delta:PCNA complex reaches a downstream Okazaki fragment, strand displacement synthesis occurs. The primer containing 5'-terminus of the downstream Okazaki fragment is folded into a single-stranded flap.7711022Pubmed1995DNA polymerase delta holoenzyme: action on single-stranded DNA and on double-stranded DNA in the presence of replicative DNA helicases.Podust, VNPodust, LMMüller, FHubscher, UBiochemistry 34:5003-1011473323Pubmed2001RPA governs endonuclease switching during processing of Okazaki fragments in eukaryotes.Bae, SHBae, KHKim, JASeo, YSNature 412:456-6111724925Pubmed2001Okazaki fragment processing: modulation of the strand displacement activity of DNA polymerase delta by the concerted action of replication protein A, proliferating cell nuclear antigen, and flap endonuclease-1.Maga, GVillani, GTillement, VStucki, MLocatelli, GASpadari, SHubscher, UProc Natl Acad Sci U S A 98:14298-303Removal of the Flap IntermediateThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>LEFT-TO-RIGHTRemoval of remaining FlapThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Processive complex:Okazaki fragments:Remaining FlapReactome DB_ID: 10727521Remaining FlapReactome DB_ID: 68467Reactome Database ID Release 7568467Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68467ReactomeR-ALL-684672Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-68467.2ChEBI61120111Reactome Database ID Release 7510727521Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727521ReactomeR-SCE-684681Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68468.1Processive complex:nicked DNA from adjacent Okazaki fragmentsReactome DB_ID: 10727523Okazaki fragment minus FlapReactome DB_ID: 68469Reactome Database ID Release 7568469Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=68469ReactomeR-ALL-684692Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-68469.2ChEBI6112011Reactome Database ID Release 7510727523Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727523ReactomeR-SCE-684701Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-68470.1ACTIVATIONFEN1RAD27P26793Reactome DB_ID: 10727528UniProt:P26793RAD27UniProtP267931EQUAL380EQUALReactome Database ID Release 7510727528Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727528ReactomeR-SCE-547451Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-54745.1GENE ONTOLOGYGO:0017108Reactome Database ID Release 7510727529Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727529Reactome Database ID Release 7510727531Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727531ReactomeR-SCE-691521Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-69152.1The remaining flap, which is too short to support RPA binding, is then processed by FEN-1. There is evidence that binding of RPA to the displaced end of the RNA-containing Okazaki fragment prevents FEN-1 from accessing the substrate. FEN-1 is a structure-specific endonuclease that cleaves near the base of the flap at a position one nucleotide into the annealed region. Biochemical studies have shown that the preferred substrate for FEN-1 consists of a one-nucleotide 3'-tail on the upstream primer in addition to the 5'-flap of the downstream primer.8824221Pubmed1996Calf RTH-1 nuclease can remove the initiator RNAs of Okazaki fragments by endonuclease activity.Murante, RSRumbaugh, JABarnes, CJNorton, JRBambara, Robert AJ Biol Chem 271:25888-978131753Pubmed1994The characterization of a mammalian DNA structure-specific endonuclease.Harrington, JJLieber, MREMBO J 13:1235-469080773Pubmed1997The FEN-1 family of structure-specific nucleases in eukaryotic DNA replication, recombination and repair.Lieber, MRBioessays 19:233-4010409700Pubmed1999A comparison of eubacterial and archaeal structure-specific 5'-exonucleases.Kaiser, MWLyamicheva, NMa, WMiller, CNeri, BFors, LLyamichev, VIJ Biol Chem 274:21387-9411825897Pubmed2002Cleavage specificity of Saccharomyces cerevisiae flap endonuclease 1 suggests a double-flap structure as the cellular substrate.Kao, HIHenricksen, LALiu, YBambara, Robert AJ Biol Chem 277:14379-8910806216Pubmed2000Coordination between the polymerase and 5'-nuclease components of DNA polymerase I of Escherichia coli.Xu, YGrindley, NDJoyce, CMJ Biol Chem 275:20949-557876218Pubmed1995DNA structural elements required for FEN-1 binding.Harrington, JJLieber, MRJ Biol Chem 270:4503-8Reactome Database ID Release 7510753083Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10753083ReactomeR-SCE-691661Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-69166.1Two endonucleases, Dna2 and flap endonuclease 1 (FEN-1), are responsible for resolving the nascent flap structure (Tsurimoto and Stillman 1991). The Dna2 endonuclease/helicase in yeast is a monomer of approximately 172 kDa. Human FEN-1 is a single polypeptide of approximately 42 kDa. Replication Protein A regulates the switching of endonucleases during the removal of the displaced flap (Tsurimoto et al.1991).7644470Pubmed1995A yeast gene required for DNA replication encodes a protein with homology to DNA helicases.Budd, MECampbell, JLProc Natl Acad Sci U S A 92:7642-67926735Pubmed1994Functional domains within FEN-1 and RAD2 define a family of structure-specific endonucleases: implications for nucleotide excision repair.Harrington, JJLieber, MRGenes Dev 8:1344-55LEFT-TO-RIGHT6.5.1Joining of adjacent Okazaki fragmentsThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>ligated okazaki fragmentReactome DB_ID: 69172Reactome Database ID Release 7569172Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=69172ReactomeR-ALL-691722Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-69172.2ChEBI61120ACTIVATIONCDC9LIG1P04819Reactome DB_ID: 10727536UniProt:P04819CDC9UniProtP048191EQUAL919EQUALReactome Database ID Release 7510727536Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727536ReactomeR-SCE-537871Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-53787.1GENE ONTOLOGYGO:0003909Reactome Database ID Release 7510727537Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727537Reactome Database ID Release 7510727539Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10727539ReactomeR-SCE-691731Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-69173.1Removal of the flap by FEN-1 leads to the generation of a nick between the 3'-end of the upstream Okazaki fragment and the 5'-end of the downstream Okazaki fragment. DNA ligase I then seals the nicks between adjacent processed Okazaki fragments to generate intact double-stranded DNA.9081985Pubmed1997Enzymes and reactions at the eukaryotic DNA replication fork.Bambara, Robert AMurante, RSHenricksen, LAJ Biol Chem 272:4647-5010959839Pubmed2000Interaction between PCNA and DNA ligase I is critical for joining of Okazaki fragments and long-patch base-excision repair.Levin, DSMcKenna, AEMotycka, TAMatsumoto, YTomkinson, AECurr Biol 10:919-228392066Pubmed1993Completion of mammalian lagging strand DNA replication using purified proteins.Turchi, JJBambara, Robert AJ Biol Chem 268:15136-419759502Pubmed1998The DNA replication fork in eukaryotic cells.Waga, SStillman, BAnnu Rev Biochem 67:721-51Reactome Database ID Release 7510753081Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10753081ReactomeR-SCE-691831Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-69183.1The key event that allows the processive synthesis on the lagging strand, is polymerase switching from pol alpha to pol delta, as on the leading strand. However, the processive synthesis on the lagging strand proceeds very differently. DNA synthesis is discontinuous, and involves the formation of short fragments called the Okazaki fragments. During the synthesis of Okazaki fragments, the RNA primer is folded into a single-stranded flap, which is removed by endonucleases. This is followed by the ligation of adjacent Okazaki fragments.Reactome Database ID Release 7510753075Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10753075ReactomeR-SCE-691861Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-69186.1Due to the antiparallel nature of DNA, DNA polymerization is unidirectional, and one strand is synthesized discontinuously. This strand is called the lagging strand. Although the polymerase switching on the lagging strand is very similar to that on the leading strand, the processive synthesis on the two strands proceeds quite differently. Short DNA fragments, about 100 bases long, called Okazaki fragments are synthesized on the RNA-DNA primers first. Strand-displacement synthesis occurs, whereby the primer-containing 5'-terminus of the adjacent Okazaki fragment is folded into a single-stranded flap structure. This flap structure is removed by endonucleases, and the adjacent Okazaki fragments are joined by DNA ligase.Reactome Database ID Release 7510753077Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10753077ReactomeR-SCE-691901Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-69190.1GENE ONTOLOGYGO:0006271Accurate and efficient genome duplication requires coordinated processes to replicate two template strands at eucaryotic replication forks. Knowledge of the fundamental reactions involved in replication fork progression is derived largely from biochemical studies of the replication of simian virus and from yeast genetic studies. Since duplex DNA forms an anti-parallel structure, and DNA polymerases are unidirectional, one of the new strands is synthesized continuously in the direction of fork movement. This strand is designated as the leading strand. The other strand grows in the direction away from fork movement, and is called the lagging strand. Several specific interactions among the various proteins involved in DNA replication underlie the mechanism of DNA synthesis, on both the leading and lagging strands, at a DNA replication fork. These interactions allow the replication enzymes to cooperate in the replication process (Hurwitz et al 1990; Brush et al 1996; Ayyagari et al 1995; Budd & Campbell 1997; Bambara et al 1997).1536007Pubmed1992A yeast chromosomal origin of DNA replication defined by multiple functional elements.Marahrens, YStillman, BScience 255:817-231976634Pubmed1990The in vitro replication of DNA containing the SV40 origin.Hurwitz, JKwong, ADLee, SHJ Biol Chem 265:18043-68594377Pubmed1996Identification of eukaryotic DNA replication proteins using simian virus 40 in vitro replication system.Brush, GSKelly, TJStillman, BMethods Enzymol 262:522-487623835Pubmed1995A mutational analysis of the yeast proliferating cell nuclear antigen indicates distinct roles in DNA replication and DNA repair.Ayyagari, RImpellizzeri, KJYoder, BLGary, SLBurgers, PMMol Cell Biol 15:4420-9Reactome Database ID Release 7510753053Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10753053ReactomeR-SCE-692391Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-69239.1The actual synthesis of DNA occurs in the S phase of the cell cycle. This includes the initiation of DNA replication, when the first nucleotide of the new strand is laid down during the synthesis of the primer. The DNA replication preinitiation events begin in late M or early G1 phase. Establishment of Sister Chromatid CohesionThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>LEFT-TO-RIGHT2.3.1.5Acetylation of SMC3 subunit of chromosomal arm associated cohesin by ESCO1 or ESCO2This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Cohesin:PDS5:WAPAL:Chromosomal ArmReactome DB_ID: 10740879Cohesin:PDS5:WAPALReactome DB_ID: 10740877PDS5PDS5AQ04264Reactome DB_ID: 10740871UniProt:Q04264PDS5UniProtQ042641EQUAL1337EQUALReactome Database ID Release 7510740871Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10740871ReactomeR-SCE-24680431Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-2468043.11Ghost homologue of WAPALReactome DB_ID: 10740875Reactome Database ID Release 7510740875Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10740875ReactomeR-SCE-24663551Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-2466355.11Cohesin ComplexReactome DB_ID: 10740869IRR1STAG1P40541Reactome DB_ID: 10740867UniProt:P40541IRR1UniProtP405411EQUAL1258EQUALReactome Database ID Release 7510740867Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10740867ReactomeR-SCE-1630161Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-163016.11SMC1SMC1AP32908Reactome DB_ID: 10740859UniProt:P32908SMC1UniProtP329081EQUAL1233EQUALReactome Database ID Release 7510740859Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10740859ReactomeR-SCE-645611Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-64561.11SMC3SMC3P47037Reactome DB_ID: 10740861UniProt:P47037SMC3UniProtP470371EQUAL1217EQUALReactome Database ID Release 7510740861Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10740861ReactomeR-SCE-1630091Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-163009.11IRR1STAG2P40541Reactome DB_ID: 107408651EQUAL1231EQUALReactome Database ID Release 7510740865Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10740865ReactomeR-SCE-1630461Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-163046.11MCD1RAD21Q12158Reactome DB_ID: 10740863UniProt:Q12158MCD1UniProtQ121581EQUAL631EQUALReactome Database ID Release 7510740863Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10740863ReactomeR-SCE-1630421Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-163042.11Reactome Database ID Release 7510740869Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10740869ReactomeR-SCE-16415051Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-1641505.11Reactome Database ID Release 7510740877Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10740877ReactomeR-SCE-24680421Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-2468042.11Sister Chromosomal ArmReactome DB_ID: 1638790chromosomeGENE ONTOLOGYGO:0005694Reactome Database ID Release 751638790Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1638790ReactomeR-ALL-16387902Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-1638790.2ChEBI233671Reactome Database ID Release 7510740879Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10740879ReactomeR-SCE-25451791Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-2545179.1Ac-CoAAcetyl coenzyme Aacetyl-CoAReactome DB_ID: 113560acetyl-CoA [ChEBI:15351]acetyl-CoAChEBICHEBI:15351Reactome Database ID Release 75113560Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113560ReactomeR-ALL-1135603Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113560.3COMPOUNDC000242Ac-Cohesin:PDS5:WAPAL:Chromosomal ArmReactome DB_ID: 107408871Ac-Cohesin:PDS5:WAPALReactome DB_ID: 10740885Ac-Cohesin ComplexReactome DB_ID: 1074088311SMC32xAcK-SMC3P47037Reactome DB_ID: 10740881105EQUALN6-acetyl-L-lysineMODMOD:00064106EQUAL1EQUAL1217EQUALReactome Database ID Release 7510740881Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10740881ReactomeR-SCE-24680501Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-2468050.1111Reactome Database ID Release 7510740883Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10740883ReactomeR-SCE-24680481Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-2468048.1111Reactome Database ID Release 7510740885Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10740885ReactomeR-SCE-24680471Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-2468047.11Reactome Database ID Release 7510740887Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10740887ReactomeR-SCE-24731531Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-2473153.1CoACoA-SHcoenzyme AReactome DB_ID: 2485002coenzyme A [ChEBI:15346]coenzyme AChEBICHEBI:15346Reactome Database ID Release 752485002Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2485002ReactomeR-ALL-24850023Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-2485002.3COMPOUNDC000102ACTIVATIONECO1ESCO1P43605Reactome DB_ID: 10740892UniProt:P43605ECO1UniProtP436051EQUAL840EQUALReactome Database ID Release 7510740892Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10740892ReactomeR-SCE-24664011Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-2466401.1GENE ONTOLOGYGO:0008080Reactome Database ID Release 7510740895Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10740895Reactome Database ID Release 7510740897Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10740897ReactomeR-SCE-24680391Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-2468039.1Acetyltransferases ESCO1 and ESCO2 are homologs of the S. cerevisiae acetyltransferase Eco1, essential for viability in yeast. ESCO1 and ESCO2 share sequence homology in the C-terminal region, consisting of a H2C2 zinc finger motif and an acetyltransferase domain (Hou and Zou 2005). Both ESCO1 and ESCO2 acetylate the cohesin subunit SMC3 on two lysine residues, K105 and K106 (Zhang et al. 2008), an important step in the establishment of sister-chromatid cohesion during the S-phase of the cell cycle. These dual acetylations on SMC3 are deacetylated by HDAC8 after the cohesin removal from chromatin for the dissociation and recycling of cohesin subunits (Deardorff et al. 2012). ESCO1 and ESCO2 differ in their N-termini, which are necessary for chromatin binding, and may perform distinct functions in sister chromatid cohesion (Hou and Zou 2005), as suggested by the study of Esco2 knockout mice (Whelan et al. 2012).18614053Pubmed2008Acetylation of Smc3 by Eco1 is required for S phase sister chromatid cohesion in both human and yeastZhang, JinglanShi, XiaominLi, YehuaKim, Beom-JunJia, JunlingHuang, ZhiweiYang, TaoFu, XiaoyongJung, Sung YunWang, YZhang, PuminKim, Seong-TaePan, XuewenQin, JMol. Cell 31:143-5122885700Pubmed2012HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycleDeardorff, Matthew ABando, MasashigeNakato, RyuichiroWatrin, ErwanItoh, TakehikoMinamino, MasashiSaitoh, KatsuyaKomata, MakikoKatou, YukiClark, DinahCole, Kathryn EDe Baere, ElfrideDecroos, ChristopheDi Donato, NataliyaErnst, SarahFrancey, Lauren JGyftodimou, YolandaHirashima, KyotaroHullings, MelanieIshikawa, YuuichiJaulin, ChristianKaur, ManinderKiyono, TLombardi, Patrick MMagnaghi-Jaulin, LMortier, Geert RNozaki, NaohitoPetersen, Michael BSeimiya, HiroyukiSiu, Victoria MSuzuki, YutakaTakagaki, KentaroWilde, Jonathan JWillems, Patrick JPrigent, ClaudeGillessen-Kaesbach, GabrieleChristianson, DWKaiser, Frank JJackson, Laird GHirota, ToruKrantz, Ian DShirahige, KatsuhikoNature 489:313-722101327Pubmed2012Cohesin acetyltransferase Esco2 is a cell viability factor and is required for cohesion in pericentric heterochromatinWhelan, GabrielaKreidl, EmanuelWutz, GordanaEgner, AlexanderPeters, Jan-MichaelEichele, GregorEMBO J. 31:71-8221111234Pubmed2010Sororin mediates sister chromatid cohesion by antagonizing WaplNishiyama, TomokoLadurner, ReneSchmitz, JuliaKreidl, EmanuelSchleiffer, AlexanderBhaskara, VenugopalBando, MasashigeShirahige, KatsuhikoHyman, Anthony AMechtler, KarlPeters, Jan-MichaelCell 143:737-4915958495Pubmed2005Two human orthologues of Eco1/Ctf7 acetyltransferases are both required for proper sister-chromatid cohesionHou, FajianZou, HuiMol. Biol. Cell 16:3908-18LEFT-TO-RIGHT2.3.1.5Acetylation of SMC3 subunit of centromeric chromatin associated cohesin by ESCO1 or ESCO2This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Cohesin:PDS5:WAPAL:CentromereReactome DB_ID: 10740905Sister CentromereReactome DB_ID: 1638792Reactome Database ID Release 751638792Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1638792ReactomeR-ALL-16387923Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-1638792.3ChEBI2336711Reactome Database ID Release 7510740905Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10740905ReactomeR-SCE-25451771Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-2545177.12Ac-Cohesin:PDS5:WAPAL:CentromereReactome DB_ID: 1074090711Reactome Database ID Release 7510740907Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10740907ReactomeR-SCE-24731491Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-2473149.12ACTIVATIONReactome Database ID Release 7510740909Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10740909ReactomeR-SCE-24731521Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-2473152.1Acetyltransferases ESCO1 and ESCO2 are homologs of the S. cerevisiae acetyltransferase Eco1, essential for viability in yeast. ESCO1 and ESCO2 share sequence homology in the C-terminal region, consisting of a H2C2 zinc finger motif and an acetyltransferase domain (Hou and Zou 2005). Both ESCO1 and ESCO2 acetylate the cohesin subunit SMC3 on two lysine residues, K105 and K106 (Zhang et al. 2008), an important step in the establishment of sister-chromatid cohesion during the S-phase of the cell cycle. Divergent N-termini of ESCO1 and ESCO2, necessary for chromatin binding, suggest that ESCO1 and ESCO2 may perform distinct functions in sister chromatid cohesion (Hou and Zou 2005). Several studies suggest that ESCO2 may be predominantly involved in acetylation of the SMC3 subunit of centromeric cohesin. A conditional targeting of Esco2 locus in mice leads to pre-implantational loss of homozygous Esco2 -/- embryos at the eight-cell stage. Prometaphase chromosomes isolated from two-cell stage Esco2 knockout embryos show marked cohesion defect at centromeres (Whelan et al. 2012). ESCO2 protein appears in the S-phase (Hou and Zou 2005, Whelan et al. 2012) and in mouse embryonic fibroblasts Esco2 predominantly localizes to pericentric heterochromatin (Whelan et al. 2012). Mutations in the ESCO2 gene (Vega et al. 2005) that impair ESCO2 acetyltransferase activity (Gordillo et al. 2008) are the cause of the Roberts syndrome, an autosomal recessive disorder characterized by craniofacial and limb abnormalities, and intellectual disability. Metaphase chromosomes of Roberts syndrome patients exhibit loss of cohesion at heterochromatic regions of centromeres and the Y chromosome, with a characteristic 'railroad track appearance' (Van den Berg and Francke 1993, Vega et al. 2005).8291532Pubmed1993Roberts syndrome: a review of 100 cases and a new rating system for severityVan Den Berg, D JFrancke, UAm. J. Med. Genet. 47:1104-2318411254Pubmed2008The molecular mechanism underlying Roberts syndrome involves loss of ESCO2 acetyltransferase activityGordillo, MiriamVega, HugoTrainer, Alison HHou, FajianSakai, NorioLuque, RicardoKayserili, HülyaBasaran, SeherSkovby, FHennekam, RCUzielli, Maria L GiovannucciSchnur, Rhonda EManouvrier, SylvieChang, SusanBlair, EdwardHurst, Jane AForzano, FrancescaMeins, MoritzSimola, Kalle O JRaas-Rothschild, AnnickSchultz, Roger AMcDaniel, Lisa DOzono, KeiichiInui, KojiZou, HuiJabs, Ethylin WangHum. Mol. Genet. 17:2172-8015821733Pubmed2005Roberts syndrome is caused by mutations in ESCO2, a human homolog of yeast ECO1 that is essential for the establishment of sister chromatid cohesionVega, HugoWaisfisz, QuintenGordillo, MiriamSakai, NorioYanagihara, ItaruYamada, Minoruvan Gosliga, DjokeKayserili, HülyaXu, ChengzheOzono, KeiichiJabs, Ethylin WangInui, KojiJoenje, HansNat. Genet. 37:468-70Reactome Database ID Release 7510754193Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10754193ReactomeR-SCE-24680521Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-2468052.1The cohesin complex loads onto chromatin in telophase, but its association with chromatin remains transient, dynamic until the S-phase of the cell cycle, presumably because the cohesin-bound NIPBL:MAU2 (SCC2:SCC4) complex promotes chromatin loading, while cohesin-bound WAPAL promotes dissociation from chromatin. Stable binding of cohesin complexes to chromatin, measured by a mean residence time on chromatin, is triggered by DNA replication in S-phase (Gerlich et al. 2006), consistent with establishment of sister chromatid cohesion. <br><br> In S-phase, acetyltransferases ESCO1 and ESCO2 acetylate the SMC3 cohesin subunit (Hou and Zou 2005, Zhang et al. 2008, Nishiyama et al. 2010, Whelan et al. 2012). The acetylation of SMC3, in addition to DNA replication and the presence of PDS5 on cohesin, facilitates the recruitment of CDCA5 (Sororin) to cohesin complexes, an essential step in the establishment of sister chromatid cohesion in mammalian cells (Rankin et al. 2005, Nishiyama et al. 2010). CDCA5 (Sororin) displaces WAPAL from PDS5, thus preventing WAPAL to interfere with the establishment of sister chromatid cohesion (Nishiyama et al. 2010). The establishment and temporal regulation of sister chromatid cohesion is necessary for equal segregation of replicated chromosomes to daughter cells. 15837422Pubmed2005Sororin, a substrate of the anaphase-promoting complex, is required for sister chromatid cohesion in vertebratesRankin, SusannahAyad, Nagi GKirschner, Marc WMol. Cell 18:185-20016890534Pubmed2006Live-cell imaging reveals a stable cohesin-chromatin interaction after but not before DNA replicationGerlich, DanielKoch, BirgitDupeux, FlorinePeters, Jan-MichaelEllenberg, JanCurr. Biol. 16:1571-8Reactome Database ID Release 7510753055Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10753055ReactomeR-SCE-692421Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SCE-69242.1GENE ONTOLOGYGO:0000084DNA synthesis occurs in the S phase, or the synthesis phase, of the cell cycle. The cell duplicates its hereditary material, and two copies of the chromosome are formed. As DNA replication continues, the E type cyclins shared by the G1 and S phases, are destroyed and the levels of the mitotic cyclins rise.