BioPAX pathway converted from "DNA replication initiation" in the Reactome database.DNA replication initiationDNA replication initiationDNA 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).2.7.7.6The primase component of DNA polymerase:primase synthesizes a 6-10 nucleotide RNA primer at the originThe primase component of DNA polymerase:primase synthesizes a 6-10 nucleotide RNA primer at the originAt 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>Converted from EntitySet in ReactomeReactome DB_ID: 305951nucleoplasmGO0005654NTP [nucleoplasm]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityCTP [nucleoplasm]GTP [nucleoplasm]UTP [nucleoplasm]ATP [nucleoplasm]Reactomehttp://www.reactome.orgChEBI17677ChEBI15996ChEBI15713ChEBI30616Reactome DB_ID: 685101DNA polymerase alpha:primase:DNA polymerase alpha:origin complex [nucleoplasm]DNA polymerase alpha:primase:DNA polymerase alpha:origin complexReactome DB_ID: 685071DNA polymerase alpha:primase [nucleoplasm]DNA polymerase alpha:primaseprimosomeDNA Pol alpha:primaseReactome DB_ID: 96688121PRIM1:PRIM2 [nucleoplasm]PRIM1:PRIM2Primase heterodimerReactome DB_ID: 684951UniProt:P49643 PRIM2PRIM2PRIM2PRIM2AFUNCTION Regulatory subunit of the DNA primase complex and component of the DNA polymerase alpha complex (also known as the alpha DNA polymerase-primase complex) which play an essential role in the initiation of DNA synthesis (PubMed:9705292, PubMed:17893144). During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1, an accessory subunit POLA2 and two primase subunits, the catalytic subunit PRIM1 and the regulatory subunit PRIM2) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1 (By similarity). The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands (PubMed:17893144). These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively (By similarity). In the primase complex, both subunits are necessary for the initial di-nucleotide formation, but the extension of the primer depends only on the catalytic subunit (PubMed:17893144). Stabilizes and modulates the activity of the catalytic subunit (By similarity).SUBUNIT Heterodimer of a catalytic subunit PRIM1 and a regulatory subunit PRIM2, also known as the DNA primase complex (PubMed:9705292, PubMed:17893144). Interacts via (C-terminus) with PRIM1 (PubMed:17893144). Component of the alpha DNA polymerase complex (also known as the alpha DNA polymerase-primase complex) consisting of four subunits: the catalytic subunit POLA1, the regulatory subunit POLA2, and the primase complex subunits PRIM1 and PRIM2 respectively (PubMed:9705292). Within the complex, POLA1 directly interacts with PRIM2 (By similarity).SIMILARITY Belongs to the eukaryotic-type primase large subunit family.Homo sapiensNCBI Taxonomy9606UniProtP49643Chain Coordinates1EQUAL509EQUALReactome DB_ID: 684971UniProt:P49642 PRIM1PRIM1PRIM1FUNCTION Catalytic subunit of the DNA primase complex and component of the DNA polymerase alpha complex (also known as the alpha DNA polymerase-primase complex) which play an essential role in the initiation of DNA synthesis (PubMed:9268648, PubMed:9705292, PubMed:17893144). During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1, an accessory subunit POLA2 and two primase subunits, the catalytic subunit PRIM1 and the regulatory subunit PRIM2) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1 (By similarity). The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands (PubMed:17893144). These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively (By similarity). In the primase complex, both subunits are necessary for the initial di-nucleotide formation, but the extension of the primer depends only on the catalytic subunit (PubMed:17893144). Can add both ribo- and deoxynucleotides during elongation of the primers (By similarity). Binds single stranded DNA (By similarity).ACTIVITY REGULATION The presence of the regulatory subunit PRIM2/p58 accelerates the kinetics of initiation and primer extension.SUBUNIT Heterodimer of a catalytic subunit PRIM1 and a regulatory subunit PRIM2, also known as the DNA primase complex (PubMed:9705292, PubMed:17893144). Interacts with PRIM2 (via C-terminus) (PubMed:17893144). Component of the alpha DNA polymerase complex (also known as the alpha DNA polymerase-primase complex) consisting of four subunits: the catalytic subunit POLA1, the regulatory subunit POLA2, and the primase complex subunits PRIM1 and PRIM2 respectively (PubMed:9705292). Within the complex, POLA1 directly interacts with PRIM2 (By similarity).MISCELLANEOUS The bound zinc ion is not a cofactor. It is bound to a zinc knuckle motif that may be involved in sequence recognition and the binding of ssDNA (By similarity).SIMILARITY Belongs to the eukaryotic-type primase small subunit family.UniProtP496421EQUAL420EQUALReactome Database ID Release 739668812Database 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=9668812ReactomeR-HSA-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-HSA-9668812.1Reactome DB_ID: 684871UniProt:P09884 POLA1POLA1POLA1POLAFUNCTION Catalytic subunit of the DNA polymerase alpha complex (also known as the alpha DNA polymerase-primase complex) which plays an essential role in the initiation of DNA synthesis. During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1, a regulatory subunit POLA2 and two primase subunits PRIM1 and PRIM2) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1. The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands. These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively. The reason this transfer occurs is because the polymerase alpha has limited processivity and lacks intrinsic 3' exonuclease activity for proofreading error, and therefore is not well suited for replicating long complexes. In the cytosol, responsible for a substantial proportion of the physiological concentration of cytosolic RNA:DNA hybrids, which are necessary to prevent spontaneous activation of type I interferon responses (PubMed:27019227).SUBUNIT Component of the alpha DNA polymerase complex (also known as the alpha DNA polymerase-primase complex) consisting of four subunits: the catalytic subunit POLA1, the regulatory subunit POLA2, and the primase complex subunits PRIM1 and PRIM2 respectively (PubMed:9705292). Interacts with PARP1; this interaction functions as part of the control of replication fork progression (PubMed:9518481). Interacts with MCM10 and WDHD1; these interactions recruit the polymerase alpha complex to the pre-replicative complex bound to DNA (PubMed:19608746). Interacts with RPA1; this interaction stabilizes the replicative complex and reduces the misincorporation rate of DNA polymerase alpha by acting as a fidelity clamp (PubMed:9214288).SUBUNIT (Microbial infection) Interacts with SV40 Large T antigen; this interaction allows viral DNA replication.SUBUNIT (Microbial infection) Interacts with herpes simplex virus 1/HHV-1 replication origin-binding protein UL9.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.PTM A 165 kDa form is probably produced by proteolytic cleavage at Lys-124.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.UniProtP098841EQUAL1462EQUALReactome DB_ID: 684931UniProt:Q14181 POLA2POLA2POLA2FUNCTION Accessory subunit of the DNA polymerase alpha complex (also known as the alpha DNA polymerase-primase complex) which plays an essential role in the initiation of DNA synthesis (PubMed:9705292). During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1, an accessory subunit POLA2 and two primase subunits, the catalytic subunit PRIM1 and the regulatory subunit PRIM2) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1 (By similarity). The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands (By similarity). These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively (By similarity).SUBUNIT Component of the alpha DNA polymerase complex (also known as the alpha DNA polymerase-primase complex) consisting of four subunits: the catalytic subunit POLA1, the regulatory subunit POLA2, and primase complex subunits PRIM1 and PRIM2 respectively (PubMed:9705292). Within the complex, POLA1 directly interacts with PRIM2/p58 (By similarity).DOMAIN The N-terminal 240 amino acids are sufficient to mediate complex formation.PTM Phosphorylated in a cell cycle-dependent manner, in G2/M phase.SIMILARITY Belongs to the DNA polymerase alpha subunit B family.UniProtQ141811EQUAL598EQUALReactome Database ID Release 7368507Database 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=68507ReactomeR-HSA-685072Reactome 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-HSA-68507.2Reactome DB_ID: 684851DNA polymerase epsilon:origin complex [nucleoplasm]DNA polymerase epsilon:origin complexReactome DB_ID: 684831DNA polymerase epsilon [nucleoplasm]DNA polymerase epsilonReactome DB_ID: 88666841UniProt:Q9NR33 POLE4POLE4POLE4FUNCTION Accessory component of the DNA polymerase epsilon complex (PubMed:10801849). Participates in DNA repair and in chromosomal DNA replication (By similarity).SUBUNIT Component of the DNA polymerase epsilon complex consisting of four subunits: the catalytic subunit POLE and the accessory subunits POLE2, POLE3 and POLE4. Interaction with POLE3 is a prerequisite for further binding with POLE and POLE2.UniProtQ9NR332EQUAL117EQUALReactome DB_ID: 684731UniProt:Q07864 POLEPOLEPOLE1POLEFUNCTION Catalytic component of the DNA polymerase epsilon complex (PubMed:10801849). Participates in chromosomal DNA replication (By similarity). Required during synthesis of the leading DNA strands at the replication fork, binds at/or near replication origins and moves along DNA with the replication fork (By similarity). Has 3'-5' proofreading exonuclease activity that corrects errors arising during DNA replication (By similarity). Involved in DNA synthesis during DNA repair (PubMed:20227374, PubMed:27573199). Along with DNA polymerase POLD1 and DNA polymerase POLK, has a role in excision repair (NER) synthesis following UV irradiation (PubMed:20227374).SUBUNIT Component of the DNA polymerase epsilon complex consisting of four subunits: the catalytic subunit POLE and the accessory subunits POLE2, POLE3 and POLE4. Interacts with RAD17 and TOPBP1.DOMAIN The DNA polymerase activity domain resides in the N-terminal half of the protein, while the C-terminus is necessary for maintenance of the complex.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.SIMILARITY Belongs to the DNA polymerase type-B family.UniProtQ078641EQUAL2286EQUALReactome DB_ID: 88666851UniProt:Q9NRF9 POLE3POLE3CHRAC17POLE3FUNCTION Accessory component of the DNA polymerase epsilon complex (PubMed:10801849). Participates in DNA repair and in chromosomal DNA replication (By similarity). Forms a complex with CHRAC1 and binds naked DNA, which is then incorporated into chromatin, aided by the nucleosome-remodeling activity of ISWI/SNF2H and ACF1 (PubMed:10801849).SUBUNIT Component of the DNA polymerase epsilon complex consisting of four subunits: the catalytic subunit POLE and the accessory subunits POLE2, POLE3 and POLE4. Interaction with POLE4 is a prerequisite for further binding with POLE and POLE2. Interacts with CHRAC1. Together with CHRAC1, ACF1 and ISWI/SNF2H proteins, it forms the ISWI chromatin-remodeling complex, CHRAC.TISSUE SPECIFICITY Expressed in all tissues tested, including, heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.UniProtQ9NRF92EQUAL147EQUALReactome DB_ID: 684821UniProt:P56282 POLE2POLE2POLE2DPE2FUNCTION Accessory component of the DNA polymerase epsilon complex (PubMed:10801849). Participates in DNA repair and in chromosomal DNA replication (By similarity).SUBUNIT Component of the DNA polymerase epsilon complex consisting of four subunits: the catalytic subunit POLE and the accessory subunits POLE2, POLE3 and POLE4.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 epsilon subunit B family.UniProtP562821EQUAL527EQUALReactome Database ID Release 7368483Database 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=68483ReactomeR-HSA-684832Reactome 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-HSA-68483.2Reactome DB_ID: 684191origin of replication [nucleoplasm]origin of replicationARSautonomously replicating sequenceoriginReactome Database ID Release 7368485Database 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=68485ReactomeR-HSA-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-HSA-68485.1Reactome Database ID Release 7368510Database 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=68510ReactomeR-HSA-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-HSA-68510.1Reactome DB_ID: 684831Reactome DB_ID: 684231RNA primer:origin duplex:DNA polymerase alpha:primase complex [nucleoplasm]RNA primer:origin duplex:DNA polymerase alpha:primase complexReactome DB_ID: 684191Reactome DB_ID: 684221RNA primer [nucleoplasm]RNA primerReactome DB_ID: 685071Reactome Database ID Release 7368423Database 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=68423ReactomeR-HSA-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-HSA-68423.1PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 68510GO0003899GO molecular functionReactome Database ID Release 7368509Database 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=68509Reactome Database ID Release 7368913Database 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=68913ReactomeR-HSA-689132Reactome 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-HSA-68913.26693436Pubmed1984DNA primase from KB cells. Characterization of a primase activity tightly associated with immunoaffinity-purified DNA polymerase-alpha.Wang, TSHu, SZKorn, DJ Biol Chem 259:1854-652.7.7.7The polymerase component of DNA polymerase alpha:primase synthesizes a 20-nucleotide primer at the originThe polymerase component of DNA polymerase alpha:primase synthesizes a 20-nucleotide primer at the originAt 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>Reactome DB_ID: 301871dTTP [ChEBI:18077]dTTPDeoxythymidine triphosphateTTPDeoxythymidine 5'-triphosphateChEBI18077Reactome DB_ID: 684231Reactome DB_ID: 296041dATP [ChEBI:16284]dATP2'-deoxyadenosine 5'-triphosphateDeoxyadenosine triphosphateDeoxyadenosine 5'-triphosphateChEBI16284Reactome DB_ID: 301851dCTP [ChEBI:16311]dCTP2'-Deoxycytidine 5'-triphosphateDeoxycytidine triphosphatedeoxycytidine 5'-triphosphateChEBI16311Reactome DB_ID: 298921dGTP [ChEBI:16497]dGTPDeoxyguanosine 5'-triphosphate2'-deoxyguanosine 5'-triphosphateDeoxyguanosine triphosphateChEBI16497Reactome DB_ID: 684251RNA primer-DNA primer:origin duplex [nucleoplasm]RNA primer-DNA primer:origin duplexReactome DB_ID: 684231Reactome DB_ID: 684241DNA primer [nucleoplasm]DNA primerReactome Database ID Release 7368425Database 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=68425ReactomeR-HSA-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-HSA-68425.1PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 68507GO0003887GO molecular functionReactome Database ID Release 7368508Database 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=68508Reactome Database ID Release 7368950Database 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=68950ReactomeR-HSA-689503Reactome 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-HSA-68950.36094569Pubmed1984Purification 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 7368952Database 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=68952ReactomeR-HSA-689522Reactome 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-HSA-68952.211395402Pubmed2002DNA primases.Frick, DNRichardson, CCAnnu Rev Biochem 70:39-80GO0006270GO biological process