期刊
NATURE COMMUNICATIONS
卷 11, 期 1, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-020-16718-3
关键词
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资金
- NIH [R01 CA197774, R01 CA227450, T32CA009503, R01 ES024872, R01 ES030335, R01 HG009299, P30 CA013696]
- Irma T. Hirschl Award
- Italian Association for Cancer Research (AIRC)
- European Molecular Biology Organisation (EMBO) Long-Term Fellowship [ALTF 366-2019]
- Swiss National Science Foundation [31003A_175444]
- European Research Council [681630]
- American Cancer Society [129182-RSG-16-043-01-DMC]
- Stand Up to Cancer Innovative Research Grant [SU2C-AACR-IRG-02-16]
Homologous recombination (HR) mediates the error-free repair of DNA double-strand breaks to maintain genomic stability. Here we characterize C17orf53/MCM8IP, an OB-fold containing protein that binds ssDNA, as a DNA repair factor involved in HR. MCM8IP-deficient cells exhibit HR defects, especially in long-tract gene conversion, occurring downstream of RAD51 loading, consistent with a role for MCM8IP in HR-dependent DNA synthesis. Moreover, loss of MCM8IP confers cellular sensitivity to crosslinking agents and PARP inhibition. Importantly, we report that MCM8IP directly associates with MCM8-9, a helicase complex mutated in primary ovarian insufficiency, and RPA1. We additionally show that the interactions of MCM8IP with MCM8-9 and RPA facilitate HR and promote replication fork progression and cellular viability in response to treatment with crosslinking agents. Mechanistically, MCM8IP stimulates the helicase activity of MCM8-9. Collectively, our work identifies MCM8IP as a key regulator of MCM8-9-dependent DNA synthesis during DNA recombination and replication. Homologous recombination (HR) is an essential DNA repair pathway for genomic stability. Here the authors show that C17orf53/MCM8IP, an OB-fold containing protein, promotes HR through direct binding and activation of the MCM8-9 helicase complex.
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