BRCA2 C-Terminal RAD51-Binding Domain Confers Resistance to DNA-Damaging Agents
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...
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| Format: | Article |
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MDPI AG
2022-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/7/4060 |
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| author | Zida Zhu Taisuke Kitano Masami Morimatsu Arisa Tanaka Ryo Morioka Xianghui Lin Koichi Orino Yasunaga Yoshikawa |
| author_facet | Zida Zhu Taisuke Kitano Masami Morimatsu Arisa Tanaka Ryo Morioka Xianghui Lin Koichi Orino Yasunaga Yoshikawa |
| author_sort | Zida Zhu |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T11:44:59Z |
| format | Article |
| id | doaj.art-f18587456c5341f9a218ae260db81cd2 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T11:44:59Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f18587456c5341f9a218ae260db81cd22023-11-30T23:26:12ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-04-01237406010.3390/ijms23074060BRCA2 C-Terminal RAD51-Binding Domain Confers Resistance to DNA-Damaging AgentsZida Zhu0Taisuke Kitano1Masami Morimatsu2Arisa Tanaka3Ryo Morioka4Xianghui Lin5Koichi Orino6Yasunaga Yoshikawa7Laboratory of Veterinary Biochemistry, School of Veterinary Medicine, Kitasato University, Aomori 034–8628, JapanLaboratory of Veterinary Biochemistry, School of Veterinary Medicine, Kitasato University, Aomori 034–8628, JapanLaboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060–0818, JapanLaboratory of Veterinary Biochemistry, School of Veterinary Medicine, Kitasato University, Aomori 034–8628, JapanLaboratory of Veterinary Biochemistry, School of Veterinary Medicine, Kitasato University, Aomori 034–8628, JapanLaboratory of Veterinary Biochemistry, School of Veterinary Medicine, Kitasato University, Aomori 034–8628, JapanLaboratory of Veterinary Biochemistry, School of Veterinary Medicine, Kitasato University, Aomori 034–8628, JapanLaboratory of Veterinary Biochemistry, School of Veterinary Medicine, Kitasato University, Aomori 034–8628, JapanBreast 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.https://www.mdpi.com/1422-0067/23/7/4060BRCA2DNA damage repairhomologous recombination repairC-terminal RAD51-binding domainX-ray irradiationmitomycin C |
| spellingShingle | Zida Zhu Taisuke Kitano Masami Morimatsu Arisa Tanaka Ryo Morioka Xianghui Lin Koichi Orino Yasunaga Yoshikawa BRCA2 C-Terminal RAD51-Binding Domain Confers Resistance to DNA-Damaging Agents International Journal of Molecular Sciences BRCA2 DNA damage repair homologous recombination repair C-terminal RAD51-binding domain X-ray irradiation mitomycin C |
| title | BRCA2 C-Terminal RAD51-Binding Domain Confers Resistance to DNA-Damaging Agents |
| title_full | BRCA2 C-Terminal RAD51-Binding Domain Confers Resistance to DNA-Damaging Agents |
| title_fullStr | BRCA2 C-Terminal RAD51-Binding Domain Confers Resistance to DNA-Damaging Agents |
| title_full_unstemmed | BRCA2 C-Terminal RAD51-Binding Domain Confers Resistance to DNA-Damaging Agents |
| title_short | BRCA2 C-Terminal RAD51-Binding Domain Confers Resistance to DNA-Damaging Agents |
| title_sort | brca2 c terminal rad51 binding domain confers resistance to dna damaging agents |
| topic | BRCA2 DNA damage repair homologous recombination repair C-terminal RAD51-binding domain X-ray irradiation mitomycin C |
| url | https://www.mdpi.com/1422-0067/23/7/4060 |
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