Abstract
Breast cancer type 2 susceptibility (BRCA2) protein is crucial for initiating DNA damage repair after chemotherapy with DNA interstrand cross-linking agents or X-ray irradiation. These treatments induce double-stranded breaks in genomic DNA. BRCA2 contains a C-terminal RAD51-binding domain (CTRBD) that interacts with RAD51-oligomer containing nucleofilaments. RAD51 nucleofilaments are essential for the homologous recombination repair of double-stranded DNA damage. In this study, we investigated the effects of expressing the CTRBD in cells exposed to X-ray irradiation and mitomycin C treatment. Surprisingly, expressing the BRCA2 CTRBD in HeLa cells increased their resistance to X-ray irradiation and mitomycin C. To determine the ability of the BRCA2 CTRBD to mediate DNA damage repair, the endogenous BRCA2 was depleted by shRNA. No significant differences were observed between the sensitivities of the BRCA2-depleted cells with or without expressing BRCA2 CTRBD. Thus, the resistance to X-ray irradiation conferred by the exogenous CTRBD required endogenous BRCA2 expression. To the best of our knowledge, our study is the first to report the ability of the BRCA2 functional domain to confer resistance to X-ray irradiation and mitomycin C treatment. This peptide may be useful in the protection of cells against X-ray irradiation or chemotherapeutic agents.
Peptide aptamer mimicking RAD51-binding domain of BRCA2 inhibits DNA damage repair and survival in Trypanosoma brucei
