A cell cycle-specific requirement for the XRCC1 BRCT II domain during mammalian DNA strand break repair

XRCC1 protein is essential for viability in mammals and is required for eff icient DNA single-strand break repair and genetic stability following DNA b ase damage. We report here that XRCC1-dependent strand break repair in G(1) phase of the cell cycle is abolished by mutations created within the XRCC1 BRCT domain that interact with DNA ligase III. In contrast, XRCC1-dependen t DNA strand break repair in S phase is largely unaffected by these mutatio ns. These data describe a cell cycle-specific role for a BRCT domain, and w e conclude that the XRCC1-DNA ligase III complex is required for DNA strand break repair in G(1) phase of the cell cycle but is dispensable for this p rocess in S phase. The S-phase DNA repair process can remove both strand br eaks induced in S phase and those that persist from G(1) and can in part co mpensate for lack of repair in G(1). This process correlates with the appea rance of XRCC1 nuclear foci that colocalize with Rad51 and may thus functio n in concert with homologous recombination.