FEATURES

FAMILY

DESCRIPTION

Also known as XRCC6_HUMAN, XRCC6, G22P1. 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). Heterodimer composed of XRCC5/Ku80 and XRCC6/Ku70 (PubMed:11493912). Component of the core long-range non-homologous end joining (NHEJ) complex (also named DNA-PK complex) composed of PRKDC, LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF (PubMed:12509254, PubMed:9742108, PubMed:12547193, PubMed:25941166, PubMed:25670504, PubMed:33854234). Additional component of the NHEJ complex includes PAXX (PubMed:25574025, PubMed:27601299, PubMed:27705800). Following autophosphorylation, PRKDC dissociates from DNA, leading to formation of the short-range NHEJ complex, composed of LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF (PubMed:33854234). The XRCC5-XRCC6 dimer also associates with NAA15, and this complex binds to the osteocalcin promoter and activates osteocalcin expression (PubMed:12145306). In addition, XRCC6 interacts with the osteoblast-specific transcription factors MSX2, RUNX2 and DLX5 (PubMed:12145306). Interacts with ELF3 (PubMed:15075319). Interacts with ATP23 (PubMed:10219089). The XRCC5-XRRC6 dimer associates in a DNA-dependent manner with APEX1 (PubMed:8621488). Binds to CDK9 isoform 2 (PubMed:20493174). Identified in a complex with DEAF1 and XRCC5 (PubMed:22442688). Interacts with DEAF1 (via the SAND domain); the interaction is direct and may be inhibited by DNA-binding (PubMed:22442688). Interacts with CLU (By similarity). 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 CYREN isoform 1 (CYREN-1) and isoform 4 (CYREN-2) (via KBM motif) (PubMed:27063109, 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). 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 HMBOX1 (PubMed:23685356). Interacts with ATF7 (PubMed:29490055). Interacts with APLF (via KBM motif) (PubMed:23689425, PubMed:27063109). Interacts with WRN (via KBM motif) (PubMed:27063109).

EXTERNAL LINKS

XRCC6

X-ray repair cross-complementing protein 6

XRCC6

Molecular Synopsis