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 (By similarity). Required for double-strand break repair and V(D)J recombination (By similarity). Also has a role in chromosome translocation (By similarity). Has a role in chromosome translocation (By similarity). The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner (By similarity). It works in the 3'-5' direction (By similarity). 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 (By similarity). Binding to DNA may be mediated by XRCC6 (By similarity). 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 (By similarity). The XRCC5-XRRC6 dimer is probably involved in stabilizing broken DNA ends and bringing them together (By similarity). The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step (By similarity). 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 (By similarity). 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 (By similarity). The XRCC5-XRRC6 dimer together with APEX1 acts as a negative regulator of transcription (By similarity). 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 (By similarity). Heterodimer composed of XRCC5/Ku80 and XRCC6/Ku70 (By similarity). 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 (By similarity). Additional component of the NHEJ complex includes PAXX (By similarity). 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 (By similarity). The XRCC5-XRCC6 dimer also associates with NAA15, and this complex binds to the osteocalcin promoter and activates osteocalcin expression (By similarity). In addition, XRCC6 interacts with the osteoblast-specific transcription factors MSX2, RUNX2 and DLX5 (By similarity). Interacts with ELF3 (By similarity). Interacts with ATP23 (By similarity). The XRCC5-XRRC6 dimer associates in a DNA-dependent manner with APEX1 (By similarity). Binds to CDK9 (By similarity). Identified in a complex with DEAF1 and XRCC5 (By similarity). Interacts with DEAF1 (via the SAND domain); the interaction is direct and may be inhibited by DNA-binding (By similarity). Interacts with CLU (PubMed:12551933). Interacts with NR4A3; the DNA-dependent protein kinase complex DNA-PK phosphorylates and activates NR4A3 and prevents NR4A3 ubiquitinylation and degradation (By similarity). Interacts with CYREN (via KBM motif) (PubMed:30017584). 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) (By similarity). 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 (By similarity). Interacts with HMBOX1 (By similarity). Interacts with ATF7 (By similarity). Interacts with APLF (via KBM motif) (By similarity). Interacts with WRN (via KBM motif) (By similarity). The XRCC5-XRCC6 dimer associates with ALKBH2. Expression increases during promyelocyte differentiation. Phosphorylation by PRKDC may enhance helicase activity. Phosphorylation of Ser-49 does not affect DNA repair. ADP-ribosylated by PARP3. Viable. Reduced number of peripheral lymphocytes, however number of erythrocytes, platelets and neutrophils are normal. Translation levels in erythrocyte precursors are normal. Belongs to the ku70 family.