NDLI: BRCA2 C-Terminal RAD51-Binding Domain Confers Resistance to DNA-Damaging Agents

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BRCA2 C-Terminal RAD51-Binding Domain Confers Resistance to DNA-Damaging Agents

Content Provider	MDPI
Author	Zhu, Zida Kitano, Taisuke Morimatsu, Masami Tanaka, Arisa Morioka, Ryo Lin, Xianghui Orino, Koichi Yoshikawa, Yasunaga
Copyright Year	2022
Description	Breast cancer type 2 susceptibility (BRCA2) protein is crucial for initiating DNA damage repair after chemotherapy with DNA interstrand crosslinking agents or X-ray irradiation, which induces DNA double-strand breaks. BRCA2 contains a C-terminal RAD51-binding domain (CTRBD) that interacts with RAD51 oligomer-containing nucleofilaments. In this study, we investigated CTRBD expression in cells exposed to X-ray irradiation and mitomycin C treatment. Surprisingly, BRCA2 CTRBD expression in HeLa cells increased their resistance to X-ray irradiation and mitomycin C. Under endogenous BRCA2 depletion using shRNA, the sensitivities of the BRCA2-depleted cells with and without the CTRBD did not significantly differ. Thus, the resistance to X-ray irradiation conferred by an exogenous CTRBD required endogenous BRCA2 expression. BRCA2 CTRBD-expressing cells demonstrated effective RAD51 foci formation and increased homologous recombination efficiency, but not nonhomologous end-joining efficiency. 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 by increased homologous recombination efficiency. Thus, this peptide may be useful for protecting cells against X-ray irradiation or chemotherapeutic agents.
Starting Page	4060
e-ISSN	14220067
DOI	10.3390/ijms23074060
Journal	International Journal of Molecular Sciences
Issue Number	7
Volume Number	23
Language	English
Publisher	MDPI
Publisher Date	2022-04-06
Access Restriction	Open
Subject Keyword	International Journal of Molecular Sciences Oncology Brca2 Dna Damage Repair Homologous Recombination Repair C-terminal Rad51-binding Domain X-ray Irradiation Mitomycin C
Content Type	Text
Resource Type	Article

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