X-ray repair cross-complementing protein 5, 86 kDa subunit of Ku antigen, ATP-dependent DNA helicase 2 subunit 2, ATP-dependent DNA helicase II 80 kDa subunit, CTC box-binding factor 85 kDa subunit, DNA repair protein XRCC5, Ku80, Ku86, Lupus Ku autoantigen protein p86, Nuclear factor IV, Thyroid-lupus autoantigen, X-ray repair complementing defective repair in Chinese hamster cells 5, CTC85, CTCBF, TLAA, XRCC5
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). 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.
