The region of XRCC1 which harbours the three most common nonsynonymous polymorphic variants, is essential for the scaffolding function of XRCC1

► The BRCT1 region in XRCC1 is vital for complex formation, recruitment to DNA damage, correct intra-nuclear localization and DNA repair. ► The R194W, R280H and R399Q SNP variants of XRCC1 show normal intra-nuclear localization. ► R280H and R399Q SNP variants of XRCC1 have reduced ability to be recruited to, or stay at, sites of DNA damage. ► The R194W, R280H and R399Q SNP variants of XRCC1 show small, but consistent differences in the repair profiles after H2O2 and MMS challenge.