FEATURES

FAMILY

DESCRIPTION

Also known as XRCC5_HUMAN, XRCC5, G22P2. Single-stranded DNA-dependent ATP-dependent helicase. Has a role in chromosome translocation. The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner. It works in the 3'-5' direction. Binding to DNA may be mediated by XRCC6. Involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination. The XRCC5/6 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. The XRCC5/6 dimer is probably involved in stabilizing broken DNA ends and bringing them together (PubMed:12145306, PubMed:20383123, PubMed:7957065, PubMed:8621488). The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step. In association with NAA15, the XRCC5/6 dimer binds to the osteocalcin promoter and activates osteocalcin expression (PubMed:20383123). The XRCC5/6 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. 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. The XRCC5/6 dimer together with APEX1 acts as a negative regulator of transcription (PubMed:8621488). 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. Heterodimer composed of XRCC5/Ku80 and XRCC6/Ku70. The dimer associates in a DNA-dependent manner with PRKDC to form the DNA-dependent protein kinase complex DNA-PK, and with the LIG4-XRCC4 complex to form the core of the non-homologous end joining (NHEJ) complex (PubMed:25941166, PubMed:25670504, PubMed:11493912, PubMed:22442688). Additional components of the NHEJ complex include NHEJ1/XLF and PAXX (PubMed:25574025, PubMed:25941166, PubMed:25670504). The dimer also associates with NAA15, and this complex displays DNA binding activity towards the osteocalcin FGF response element (OCFRE) (PubMed:12145306). In addition, XRCC5 binds to the osteoblast-specific transcription factors MSX2 and RUNX2 (PubMed:12145306). Interacts with ELF3 (PubMed:15075319). May interact with APLF (PubMed:17353262, PubMed:17396150). The XRCC5/XRCC6 dimer associates in a DNA-dependent manner with APEX1 (PubMed:8621488). Identified in a complex with DEAF1 and XRCC6. Interacts with NR4A3; the DNA-dependent protein kinase complex DNA-PK phosphorylates and activates NR4A3 and prevents NR4A3 ubiquitinylation and degradation (PubMed:25852083). Interacts with RNF138 (PubMed:26502055). Interacts with CYREN isoform 1 (CYREN-1) and isoform 4 (CYREN-2) (PubMed:24610814, PubMed:28959974). Interacts (via N-terminus) with HSF1 (via N-terminus); this interaction is direct and prevents XRCC5/XRCC6 heterodimeric binding and non-homologous end joining (NHEJ) repair activities induced by ionizing radiation (IR) (PubMed:26359349). Interacts with DHX9; this interaction occurs in a RNA-dependent manner (PubMed:14704337). Part of the HDP-RNP complex composed of at least HEXIM1, PRKDC, XRCC5, XRCC6, paraspeckle proteins (SFPQ, NONO, PSPC1, RBM14, and MATR3) and NEAT1 RNA (PubMed:28712728). Interacts with ERCC6 (PubMed:26030138). Interats with ATF7 (PubMed:29490055).

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EXTERNAL LINKS

XRCC5

X-ray repair cross-complementing protein 5

ligandability Mutations

XRCC5

Molecular Synopsis