Central Role for the XRCC1 BRCT I Domain in Mammalian DNA Single-Strand Break Repair

AUTOR(ES)

Taylor, Richard M.

FONTE

American Society for Microbiology

RESUMO

The DNA single-strand break repair (SSBR) protein XRCC1 is required for genetic stability and for embryonic viability. XRCC1 possesses two BRCA1 carboxyl-terminal (BRCT) protein interaction domains, denoted BRCT I and II. BRCT II is required for SSBR during G1 but is dispensable for this process during S/G2 and consequently for cell survival following DNA alkylation. Little is known about BRCT I, but this domain has attracted considerable interest because it is the site of a genetic polymorphism that epidemiological studies have associated with altered cancer risk. We report that the BRCT I domain comprises the evolutionarily conserved core of XRCC1 and that this domain is required for efficient SSBR during both G1 and S/G2 cell cycle phases and for cell survival following treatment with methyl methanesulfonate. However, the naturally occurring human polymorphism in BRCT I supported XRCC1-dependent SSBR and cell survival after DNA alkylation equally well. We conclude that while the BRCT I domain is critical for XRCC1 to maintain genetic integrity and cell survival, the polymorphism does not impact significantly on this function and therefore is unlikely to impact significantly on susceptibility to cancer.

Documentos Relacionados

• Mutations in hamster single-strand break repair gene XRCC1 causing defective DNA repair.
• A Cell Cycle-Specific Requirement for the XRCC1 BRCT II Domain during Mammalian DNA Strand Break Repair
• Interference of papillomavirus E6 protein with single-strand break repair by interaction with XRCC1
• Mutation of a BRCT domain selectively disrupts DNA single-strand break repair in noncycling Chinese hamster ovary cells
• Genetic Requirements for the Single-Strand Annealing Pathway of Double-Strand Break Repair in Saccharomyces Cerevisiae