| RRC ID |
71955
|
| 著者 |
Zhu Z, Kitano T, Morimatsu M, Tanaka A, Morioka R, Lin X, Orino K, Yoshikawa Y.
|
| タイトル |
BRCA2 C-Terminal RAD51-Binding Domain Confers Resistance to DNA-Damaging Agents.
|
| ジャーナル |
Int J Mol Sci
|
| Abstract |
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.
|
| 巻・号 |
23(7)
|
| 公開日 |
2022-4-6
|
| DOI |
10.3390/ijms23074060
|
| PII |
ijms23074060
|
| PMID |
35409418
|
| PMC |
PMC9000072
|
| MeSH |
BRCA2 Protein / genetics
BRCA2 Protein / metabolism
DNA
DNA Damage
DNA Repair
HeLa Cells
Humans
Mitomycin* / pharmacology
Rad51 Recombinase* / genetics
Rad51 Recombinase* / metabolism
|
| IF |
4.556
|
| リソース情報 |
| ヒト・動物細胞 |
HeLa(RCB0007)
Hep G2
293T(RCB2202) |
