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).
