XRCC5
The protein encoded by this gene is the 80-kilodalton subunit of the Ku heterodimer protein which is also known as ATP-dependant DNA helicase II or DNA repair protein XRCC5. Ku is the DNA-binding component of the DNA-dependent protein kinase, and it functions together with the DNA ligase IV-XRCC4 complex in the repair of DNA double-strand break by non-homologous end joining and the completion of V(D)J recombination events. This gene functionally complements Chinese hamster xrs-6, a mutant defective in DNA double-strand break repair and in ability to undergo V(D)J recombination. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity. [provided by RefSeq, Jul 2008]
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).
Required for double-strand break repair and V(D)J recombination (PubMed:7957065, PubMed:8621488, PubMed:12145306, PubMed:11493912).
Also has a role in chromosome translocation (PubMed:7957065, 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:12145306, PubMed:11493912).
It works in the 3'-5' direction (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:12145306, PubMed:11493912).
Binding to DNA may be mediated by XRCC6 (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:20383123, PubMed:11493912).
The XRCC5-XRRC6 dimer is probably involved in stabilizing broken DNA ends and bringing them together (PubMed:7957065, PubMed:8621488, PubMed:12145306, PubMed:20383123).
The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step (PubMed:7957065, PubMed:8621488, PubMed:12145306, PubMed:20383123).
The XRCC5-XRRC6 dimer 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).
XRCC5 probably acts as the catalytic subunit of 5'-dRP activity, and 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).
As part of the DNA-PK complex, involved in the early steps of ribosome assembly by promoting the processing of precursor rRNA into mature 18S rRNA in the small-subunit processome (PubMed:32103174).
Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome (PubMed:32103174).
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).
Biological Process
Biological Process activation of innate immune response Source:UniProtKB1 Publication
Biological Process brain development Source:Ensembl
Biological Process cellular hyperosmotic salinity response Source:Ensembl
Biological Process cellular response to DNA damage stimulus Source:UniProtKB1 Publication
Biological Process cellular response to fatty acid Source:Ensembl
Biological Process cellular response to gamma radiation Source:UniProtKB1 Publication
Biological Process cellular response to leukemia inhibitory factor Source:Ensembl
Biological Process cellular response to X-ray Source:GO_Central1 Publication
Biological Process DNA recombination Source:ProtInc1 Publication
Biological Process double-strand break repair Source:BHF-UCL1 Publication
Biological Process double-strand break repair via nonhomologous end joining Source:UniProtKB1 Publication
Biological Process hematopoietic stem cell differentiation Source:Ensembl
Biological Process hematopoietic stem cell proliferation Source:Ensembl
Biological Process innate immune response Source:UniProtKB-KW
Biological Process negative regulation of DNA-templated transcription Source:UniProtKB1 Publication
Biological Process negative regulation of t-circle formation Source:BHF-UCL1 Publication
Biological Process neurogenesis Source:Ensembl
Biological Process positive regulation of catalytic activity Source:BHF-UCL1 Publication
Biological Process positive regulation of neurogenesis Source:Ensembl
Biological Process positive regulation of protein kinase activity Source:CAFA1 Publication
Biological Process positive regulation of telomerase activity Source:BHF-UCL1 Publication
Biological Process positive regulation of telomere maintenance via telomerase Source:BHF-UCL1 Publication
Biological Process protein localization to chromosome, telomeric region Source:BHF-UCL1 Publication
Biological Process recombinational repair Source:ComplexPortal1 Publication
Biological Process regulation of smooth muscle cell proliferation Source:UniProtKB1 Publication
Biological Process regulation of telomere maintenance Source:BHF-UCL3 Publications
Biological Process response to xenobiotic stimulus Source:Ensembl
Biological Process small-subunit processome assembly Source:UniProtKB1 Publication
Biological Process telomere maintenance Source:GO_Central1 Publication
PTM
ADP-ribosylated by PARP3.
Phosphorylated on serine residues. Phosphorylation by PRKDC may enhance helicase activity.
Sumoylated.
Ubiquitinated by RNF8 via 'Lys-48'-linked ubiquitination following DNA damage, leading to its degradation and removal from DNA damage sites (PubMed:22266820).
Ubiquitinated by RNF138, leading to remove the Ku complex from DNA breaks (PubMed:26502055).
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Datasheet