XRCC5

DNA-binding protein critical for the DNA damage response, specifically in repairing double-strand breaks (DSBs) via the classical non-homologous end joining (NHEJ) pathway. It forms a heterodimer with XRCC6 (Ku70), creating the Ku70:Ku80 heterodimer (Ku complex), which serves as a DNA end-binding complex. It primarily binds DSBs and recruits essential repair factors, assembling the core long-range NHEJ complex to facilitate the alignment and ligation of broken DNA ends. This pathway ensures the rapid repair of cytotoxic and mutagenic DSBs and contributes to the generation of diversity in T-cell receptors and antibodies through mechanisms such as V(D)J recombination. Likely acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRP lyase), catalyzing the beta-elimination of the 5'-deoxyribose-5-phosphate at abasic sites near DSBs. This activity cleans the termini of abasic sites, a common form of nucleotide damage, preparing broken ends for ligation. It may also possess 3'-5' DNA helicase activity, although this has not been confirmed in vivo, and its physiological significance remains unclear. Beyond DNA repair, the protein contributes to telomere maintenance. It is also implicated in transcriptional regulation, acting as a cofactor for various transcription factors. It 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. Can also bind RNAs and recruits PRKDC to a wide range of cellular RNAs, including the U3 small nucleolar RNA, playing a role in the biogenesis of ribosomal RNAs..

Function from UniProtKB (P13010), read 2026-09-23. CC BY 4.0.