Involvement of BRCA2 BRC Repeats in RAD51 Mediated DNA Repair

摘要

Mutations in the BRCA2 gene have been found in many familial breast cancers. Cells deficient for functional BRCA2 show various cellular abnormalities including increased sensitivity to genotoxic agents, accumulation of DNA double-strand breaks, chromosome abnormalities, and changes in cell cycle checkpoint and apoptotic responses. These observations suggest a role for BRCA2 in DNA repair. This postulation was further supported by data showing that BRCA2 interacts with RAD51, a protein involved in DNA recombination repair. RAD51 associates with BRCA2 through the highly conserved BRC repeats within the middle region of the BRCA2 protein. We have shown that ectopic expression of the BRC repeat in MCF-7 cells resulted in increased cellular sensitivity to radiation, an inability to form RAD51 radiation foci, and a loss of radiation-induced G2/M checkpoint control.