Search results for XRCC6

Showing 20 results out of 26

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Species

Types

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Reaction types

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Protein (5 results from a total of 5)

Identifier: R-HSA-58272
Species: Homo sapiens
Compartment: nucleoplasm
Primary external reference: UniProt: XRCC6: P12956
Identifier: R-HSA-6801312
Species: Homo sapiens
Compartment: secretory granule lumen
Primary external reference: UniProt: XRCC6: P12956
Identifier: R-HSA-6801300
Species: Homo sapiens
Compartment: ficolin-1-rich granule lumen
Primary external reference: UniProt: XRCC6: P12956
Identifier: R-HSA-3134813
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: XRCC6: P12956
Identifier: R-HSA-6806444
Species: Homo sapiens
Compartment: extracellular region
Primary external reference: UniProt: P12956

Complex (6 results from a total of 12)

Identifier: R-HSA-75905
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-5686711
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-75906
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-75907
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-5687152
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-5687154
Species: Homo sapiens
Compartment: nucleoplasm

Reaction (6 results from a total of 6)

Identifier: R-HSA-5686924
Species: Homo sapiens
Compartment: nucleoplasm
DCLRE1C (ARTEMIS) forms a stable complex with PRKDC (DNA-PKcs), even in the absence of DNA ends (Ma et al. 2002). Autophosphorylation of PRKDC as well as ATM-mediated phosphorylation of DCLRE1C are not prerequisites for the interaction of PRKDC and DCLRE1C (Ding et al.2003).
Identifier: R-HSA-5693574
Species: Homo sapiens
Compartment: nucleoplasm
A complex consisting of XRCC4 homodimer and DNA ligase IV (LIG4) (Sibanda et al. 2001) is recruited to the synaptic complex consisting of PRKDC (DNA-PKcs), XRCC5, XRCC6, DCLRE1C (ARTEMIS) and ligatable DNA double strand break (DSB) ends (Critchlow and Jackson 1997, Leber et al. 1998, Malu et al. 2012). XRCC4 directly interacts with XRCC5:XRCC6 (McElhinny et al. 2000, Hsu et al. 2002), while LIG4 directly interacts with PRKDC (Hsu et al. 2002) and DCLRE1C (Malu et al. 2012). NHEJ1 (XLF) homodimer binds XRCC4 and is recruited to DNA DSBs together with XRCC4 and LIG4, where it acts as a facilitator of LIG4 activity (Ahnesorg et al. 2006, Buck et al. 2006, Tsai et al. 2007, Li et al. 2008). DNA polymerases mu (POLM) or lambda (POLL) are recruited to DNA DSBs through interaction with the Ku complex (XRCC5:XRCC6) and XRCC4 (Mahajan et al. 2002, Lee et al. 2004, Fan and Wu 2004).
Identifier: R-HSA-5693599
Species: Homo sapiens
Compartment: nucleoplasm
Ionizing radiation (IR) induces single-strand breaks, i.e., cleavage of the phosphodiester backbone. When two single-strand breaks occur within approximately 10 base pairs, a DNA double-strand break (DSB) results. IR-induced DSBs are complex DNA damage lesions, frequently containing base damage, 5'-OH groups, and 3'-hydroxy or phosphoglycolate groups that must be removed prior to ligation in the final step of NHEJ (Friedberg et al, 1995; Nikjoo et al, 2001; Valerie and Povirk, 2003). The Ku70/80 heterodimer (XRCC5:XRCC6) (Walker et al., 2001) binds to the ends of the double-strand break. Ku can translocate inwards from the site of the break in an ATP-independent manner (reviewed in Dynan and Yoo, 1998). Binding of XRCC5:XRCC6 to DNA DSBs competes away the MRN complex and associated proteins from the DNA DSB (Sun et al. 2012).
Identifier: R-HSA-5693615
Species: Homo sapiens
Compartment: nucleoplasm
DNA-PKcs (PRKDC) is recruited to the Ku70:Ku80:DNA double strand break ends complex (XRCC5:XRCC6:DNA DSBs) (Gottlieb and Jackson, 1993), causing Ku to translocate inwards (away from the break) approximately 10 bp (Yoo and Dynan, 1999). This forms the DNA-PK complex (DNA-PKcs plus Ku70/Ku80) at each end of the DSB. Two DNA-PK complexes, one on either side of the DSB, interact to bring the DNA ends together.
Identifier: R-HSA-5687360
Species: Homo sapiens
Compartment: nucleoplasm
DNA polymerases mu (POLM) and lambda (POLL) facilitate non-homologous end joining (NHEJ) of DNA double strand breaks (DSBs) by filling single strand (ss) gaps (usually 1- or 2- nucleotide gaps) present at DNA DSB ends positioned for ligation in the synaptic complex containing XRCC5:XRCC6 (Ku), PRKDC (DNA-PKcs), DCLRE1C (ARTEMIS), XRCC4:LIG4 and NHEJ1 (XLF) (Mahajan et al. 2002, Lee et al. 2004, Fan and Wu 2004, McElhinny et al. 2005, Davis et al. 2008).
Identifier: R-HSA-5693604
Species: Homo sapiens
Compartment: nucleoplasm
The DNA ligase complex composed of DNA ligase 4 (LIG4) and the XRCC4 homodimer (Sibanda et al. 2000) catalyzes ligation of DNA double strand break (DSB) ends during non-homologous end joining (NHEJ). The XRCC4:LIG4 complex is recruited to NHEJ sites through interaction of its subunits with XRCC5:XRCC6 (Ku complex), PRKDC (DNA-PKcs) and DCLRE1C (ARTEMIS) (McElhinny et al. 2000, Hsu et al. 2002, Malu et al. 2012). Phosphorylation of XRCC4 by PRKDC may regulate the activity of the ligase complex (Lee et al. 2004). XRCC4:LIG4 can ligate incompatible DNA DSB ends, and may also ligate across single nucleotide gaps (Gu et al. 2007). The presence of the accessory protein NHEJ1 (XLF) facilitates XRCC4:LIG4 ligase activity, especially at mismatched DNA DSB ends (Ahnesorg et al. 2006, Buck et al. 2006, Tsai et al. 2007). Depending on other types of DNA damage present at DNA DSBs, NHEJ can result in error-free products, produce dsDNA with microdeletions and/or mismatched bases, or result in translocations (reviewed by Povirk 2012).

Pathway (2 results from a total of 2)

Identifier: R-HSA-5693532
Species: Homo sapiens
Compartment: nucleoplasm
Double-strand breaks (DSBs), one of the most deleterious types of DNA damage along with interstrand crosslinks, are caused by ionizing radiation or certain chemicals such as bleomycin. DSBs also occur physiologically, during the processes of DNA replication, meiotic exchange, and V(D)J recombination.

DSBs are sensed (detected) by the MRN complex. Binding of the MRN complex to the DSBs usually triggers ATM kinase activation, thus initiating the DNA double strand break response. ATM phosphorylates a number of proteins involved in DNA damage checkpoint signaling, as well as proteins directly involved in the repair of DNA DSBs. DSBs are repaired via homology directed repair (HDR) or via nonhomologous end-joining (NHEJ).

HDR requires resection of DNA DSB ends. Resection creates 3'-ssDNA overhangs which then anneal with a homologous DNA sequence. This homologous sequence can then be used as a template for DNA repair synthesis that bridges the DSB. HDR preferably occurs through the error-free homologous recombination repair (HRR), but can also occur through the error-prone single strand annealing (SSA), or the least accurate microhomology-mediated end joining (MMEJ). MMEJ takes place when DSB response cannot be initiated.

While HRR is limited to actively dividing cells with replicated DNA, error-prone NHEJ pathway functions at all stages of the cell cycle, playing the predominant role in both the G1 phase and in S-phase regions of DNA that have not yet replicated. During NHEJ, the Ku70:Ku80 heterodimer (also known as the Ku complex or XRCC5:XRCC6) binds DNA DSB ends, competing away the MRN complex and preventing MRN-mediated resection of DNA DSB ends. The catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs, PRKDC) is then recruited to DNA-bound Ku to form the DNA-PK holoenzyme. Two DNA-PK complexes, one at each side of the break, bring DNA DSB ends together, joining them in a synaptic complex. DNA-PK complex recruits DCLRE1C (ARTEMIS) to DNA DSB ends, leading to trimming of 3'- and 5'-overhangs at the break site, followed by ligation.

For review of this topic, please refer to Ciccia and Elledge 2010.

Identifier: R-HSA-5693571
Species: Homo sapiens
Compartment: nucleoplasm
The nonhomologous end joining (NHEJ) pathway is initiated in response to the formation of DNA double-strand breaks (DSBs) induced by DNA-damaging agents, such as ionizing radiation. DNA DSBs are recognized by the MRN complex (MRE11A:RAD50:NBN), leading to ATM activation and ATM-dependent recruitment of a number of DNA damage checkpoint and repair proteins to DNA DSB sites (Lee and Paull 2005). The ATM phosphorylated MRN complex, MDC1 and H2AFX-containing nucleosomes (gamma-H2AX) serve as scaffolds for the formation of nuclear foci known as ionizing radiation induced foci (IRIF) (Gatei et al. 2000, Paull et al. 2000, Stewart et al. 2003, Stucki et al. 2005). Ultimately, both BRCA1:BARD1 heterodimers and TP53BP1 (53BP1) are recruited to IRIF (Wang et al. 2007, Pei et al. 2011, Mallette et al. 2012), which is necessary for ATM-mediated CHEK2 activation (Wang et al. 2002, Wilson et al. 2008). In G1 cells, TP53BP1 promotes NHEJ by recruiting RIF1 and PAX1IP, which displaces BRCA1:BARD1 and associated proteins from the DNA DSB site and prevents resection of DNA DSBs needed for homologous recombination repair (HRR) (Escribano-Diaz et al. 2013, Zimmermann et al. 2013, Callen et al. 2013). TP53BP1 also plays an important role in ATM-mediated phosphorylation of DCLRE1C (ARTEMIS) (Riballo et al. 2004, Wang et al. 2014). Ku70:Ku80 heterodimer (also known as the Ku complex or XRCC5:XRCC6) binds DNA DSB ends, competing away the MRN complex and preventing MRN-mediated resection of DNA DSB ends (Walker et al. 2001, Sun et al. 2012). The catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs, PRKDC) is then recruited to DNA-bound Ku to form the DNA-PK holoenzyme. Two DNA-PK complexes, one at each side of the break, bring DNA DSB ends together, joining them in a synaptic complex (Gottlieb 1993, Yoo and Dynan 2000). DNA-PK complex recruits DCLRE1C (ARTEMIS) to DNA DSB ends (Ma et al. 2002). PRKDC-mediated phosphorylation of DCLRE1C, as well as PRKDC autophosphorylation, enables DCLRE1C to trim 3'- and 5'-overhangs at DNA DSBs, preparing them for ligation (Ma et al. 2002, Ma et al. 2005, Niewolik et al. 2006). The binding of inositol phosphate may additionally stimulate the catalytic activity of PRKDC (Hanakahi et al. 2000). Other factors, such as polynucleotide kinase (PNK), TDP1 or TDP2 may remove unligatable damaged nucleotides from 5'- and 3'-ends of the DSB, converting them to ligatable substrates (Inamdar et al. 2002, Gomez-Herreros et al. 2013). DNA ligase 4 (LIG4) in complex with XRCC4 (XRCC4:LIG4) is recruited to ligatable DNA DSB ends together with the XLF (NHEJ1) homodimer and DNA polymerases mu (POLM) and/or lambda (POLL) (McElhinny et al. 2000, Hsu et al. 2002, Malu et al. 2002, Ahnesorg et al. 2006, Mahajan et al. 2002, Lee et al. 2004, Fan and Wu 2004). After POLL and/or POLM fill 1- or 2-nucleotide long single strand gaps at aligned DNA DSB ends, XRCC4:LIG4 performs the ligation of broken DNA strands, thus completing NHEJ. The presence of NHEJ1 homodimer facilitates the ligation step, especially at mismatched DSB ends (Tsai et al. 2007). Depending on other types of DNA damage present at DNA DSBs, NHEJ can result in error-free products, produce dsDNA with microdeletions and/or mismatched bases, or result in translocations (reviewed by Povrik et al. 2012).

Icon (1 results from a total of 1)

Species: Homo sapiens
Complex of X-ray repair cross-complementing proteins 5 and 6, also known as XRCC5 and XRCC6
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