XRCC6
UniProt ID: P12956
Entrez ID: 2547
Protein name: X-ray repair cross-complementing protein 6 (EC 3.6.4.-) (EC 4.2.99.-) (5'-deoxyribose-5-phosphate lyase Ku70) (5'-dRP lyase Ku70) (70 kDa subunit of Ku antigen) (ATP-dependent DNA helicase 2 subunit 1) (ATP-dependent DNA helicase II 70 kDa subunit) (CTC box-binding factor 75 kDa subunit) (CTC75) (CTCBF) (DNA repair protein XRCC6) (Lupus Ku autoantigen protein p70) (Ku70) (Thyroid-lupus autoantigen) (TLAA) (X-ray repair complementing defective repair in Chinese hamster cells 6)
External links: UniprotKB HGNC RefSeq COSMIC
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FUNCTION: Single-stranded DNA-dependent ATP-dependent helicase that plays a key role in DNA non-homologous end joining (NHEJ) by recruiting DNA-PK to DNA (PubMed:7957065, PubMed:8621488, PubMed:12145306, PubMed:11493912, PubMed:20493174, PubMed:2466842, PubMed:9742108). Required for double-strand br...
FUNCTION: Single-stranded DNA-dependent ATP-dependent helicase that plays a key role in DNA non-homologous end joining (NHEJ) by recruiting DNA-PK to DNA (PubMed:7957065, PubMed:8621488, PubMed:12145306, PubMed:11493912, PubMed:20493174, PubMed:2466842, PubMed:9742108). Required for double-strand break repair and V(D)J recombination (PubMed:7957065, PubMed:8621488, PubMed:12145306, PubMed:11493912, PubMed:20493174, PubMed:2466842, PubMed:9742108). Also has a role in chromosome translocation (PubMed:7957065, PubMed:8621488, PubMed:12145306, PubMed:11493912, PubMed:20493174, PubMed:2466842, PubMed:9742108). Has a role in chromosome translocation (PubMed:7957065, PubMed:20493174, PubMed:2466842, PubMed:9742108, PubMed:8621488, PubMed:12145306, PubMed:11493912). The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner (PubMed:7957065, PubMed:8621488, PubMed:20493174, PubMed:2466842, PubMed:9742108, PubMed:12145306, PubMed:11493912). It works in the 3'-5' direction (PubMed:20493174, PubMed:2466842, PubMed:9742108, PubMed:7957065, PubMed:8621488, PubMed:12145306, PubMed:11493912). During NHEJ, the XRCC5-XRRC6 dimer performs the recognition step: it recognizes and binds to the broken ends of the DNA and protects them from further resection (PubMed:7957065, PubMed:8621488, PubMed:20493174, PubMed:2466842, PubMed:9742108, PubMed:12145306, PubMed:11493912). Binding to DNA may be mediated by XRCC6 (PubMed:20493174, PubMed:2466842, PubMed:9742108, PubMed:7957065, PubMed:8621488, PubMed:12145306, PubMed:11493912). The XRCC5-XRRC6 dimer acts as regulatory subunit of the DNA-dependent protein kinase complex DNA-PK by increasing the affinity of the catalytic subunit PRKDC to DNA by 100-fold (PubMed:7957065, PubMed:8621488, PubMed:12145306, PubMed:11493912, PubMed:20493174, PubMed:2466842, PubMed:9742108). The XRCC5-XRRC6 dimer is probably involved in stabilizing broken DNA ends and bringing them together (PubMed:7957065, PubMed:8621488, PubMed:12145306, PubMed:11493912, PubMed:20493174, PubMed:2466842, PubMed:9742108). The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step (PubMed:7957065, PubMed:8621488, PubMed:12145306, PubMed:11493912, PubMed:20493174, PubMed:2466842, PubMed:9742108). Probably also acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRP lyase), by catalyzing the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site near double-strand breaks (PubMed:20383123). 5'-dRP lyase activity allows to 'clean' the termini of abasic sites, a class of nucleotide damage commonly associated with strand breaks, before such broken ends can be joined (PubMed:20383123). The XRCC5-XRRC6 dimer together with APEX1 acts as a negative regulator of transcription (PubMed:8621488). In association with NAA15, the XRCC5-XRRC6 dimer binds to the osteocalcin promoter and activates osteocalcin expression (PubMed:12145306). Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway (PubMed:28712728). {ECO:0000269|PubMed:11493912, ECO:0000269|PubMed:12145306, ECO:0000269|PubMed:20383123, ECO:0000269|PubMed:20493174, ECO:0000269|PubMed:2466842, ECO:0000269|PubMed:28712728, ECO:0000269|PubMed:7957065, ECO:0000269|PubMed:8621488, ECO:0000269|PubMed:9742108}.
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GO - Biological processes (BP):
activation of innate immune response [GO:0002218]; cellular response to gamma radiation [GO:0071480]; cellular response to X-ray [GO:0071481]; DNA ligation [GO:0006266]; double-strand break repair via classical nonhomologous end joining [GO:0097680]; double-strand break repair via nonhomologous end ...
activation of innate immune response [GO:0002218]; cellular response to gamma radiation [GO:0071480]; cellular response to X-ray [GO:0071481]; DNA ligation [GO:0006266]; double-strand break repair via classical nonhomologous end joining [GO:0097680]; double-strand break repair via nonhomologous end joining [GO:0006303]; innate immune response [GO:0045087]; negative regulation of transcription, DNA-templated [GO:0045892]; positive regulation of lymphocyte differentiation [GO:0045621]; positive regulation of protein kinase activity [GO:0045860]; positive regulation of transcription, DNA-templated [GO:0045893]; positive regulation of transcription by RNA polymerase II [GO:0045944]; recombinational repair [GO:0000725]; regulation of smooth muscle cell proliferation [GO:0048660]; telomere maintenance [GO:0000723]
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GO - Molecular function (MF):
5'-deoxyribose-5-phosphate lyase activity [GO:0051575]; ATP binding [GO:0005524]; ATP-dependent activity, acting on DNA [GO:0008094]; cyclin binding [GO:0030332]; damaged DNA binding [GO:0003684]; DNA binding [GO:0003677]; DNA helicase activity [GO:0003678]; double-stranded DNA binding [GO:0003690];...
5'-deoxyribose-5-phosphate lyase activity [GO:0051575]; ATP binding [GO:0005524]; ATP-dependent activity, acting on DNA [GO:0008094]; cyclin binding [GO:0030332]; damaged DNA binding [GO:0003684]; DNA binding [GO:0003677]; DNA helicase activity [GO:0003678]; double-stranded DNA binding [GO:0003690]; hydrolase activity [GO:0016787]; protein-containing complex binding [GO:0044877]; protein C-terminus binding [GO:0008022]; RNA binding [GO:0003723]; scaffold protein binding [GO:0097110]; telomeric DNA binding [GO:0042162]; transcription cis-regulatory region binding [GO:0000976]
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GO - Cellular component (CC):
chromosome, telomeric region [GO:0000781]; cytosol [GO:0005829]; DNA-dependent protein kinase complex [GO:0070418]; extracellular region [GO:0005576]; ficolin-1-rich granule lumen [GO:1904813]; Ku70:Ku80 complex [GO:0043564]; membrane [GO:0016020]; nonhomologous end joining complex [GO:0070419]; nuc...
chromosome, telomeric region [GO:0000781]; cytosol [GO:0005829]; DNA-dependent protein kinase complex [GO:0070418]; extracellular region [GO:0005576]; ficolin-1-rich granule lumen [GO:1904813]; Ku70:Ku80 complex [GO:0043564]; membrane [GO:0016020]; nonhomologous end joining complex [GO:0070419]; nuclear telomere cap complex [GO:0000783]; nucleolus [GO:0005730]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; protein-containing complex [GO:0032991]; protein-DNA complex [GO:0032993]; secretory granule lumen [GO:0034774]; transcription regulator complex [GO:0005667]
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XRCC6
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*NOTE: the Kaplan plots were collected from OncoLnc