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 efficient DNA single-strand break repair and genetic stability following DNA base 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-dependent DNA strand break repair in S phase is largely unaffected by these mutations. These data describe a cell cycle-specific role for a BRCT domain, and we 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 process in S phase. The S-phase DNA repair process can remove both strand breaks induced in S phase and those that persist from G(1) and can in part compensate for lack of repair in G(1). This process correlates with the appearance of XRCC1 nuclear foci that colocalize with Rad51 and may thus function in concert with homologous recombination.
Taylor
R M
RM
School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom.
Moore
D J
DJ
Whitehouse
J
J
Johnson
P
P
Caldecott
K W
KW
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics*; D002467:Cell Nucleus / Q000737:chemistry / Q000187:drug effects / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics; D006224:Cricetinae; D004249:DNA Damage / Q000187:drug effects / Q000235:genetics*; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000378:metabolism; D004260:DNA Repair / Q000235:genetics*; D004277:DNA, Single-Stranded / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D005020:Ethyl Methanesulfonate / Q000494:pharmacology; D016193:G1 Phase / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D000075223:Poly-ADP-Ribose Binding Proteins; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051135:Rad51 Recombinase; D016196:S Phase / Q000235:genetics; D000076105:X-ray Repair Cross Complementing Protein 1; D029867:Xenopus Proteins
D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D029867:Xenopus Proteins; D005020:Ethyl Methanesulfonate; C495153:RAD51 protein, human; D051135:Rad51 Recombinase; D011088:DNA Ligases; D000072481:DNA Ligase ATP; C000618816:DNA ligase III alpha protein, Xenopus; C000618817:LIG3 protein, human