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USP13 regulates the replication stress response by deubiquitinating TopBP1.

ABSTRACT: The DNA replication stress-induced checkpoint activated through the TopBP1-ATR axis is important for maintaining genomic stability. However, the regulation of TopBP1 in DNA-damage responses remains unclear. In this study, we identify the deubiquitinating enzyme (DUB) USP13 as an important regulator of TopBP1. Mechanistically, USP13 binds to TopBP1 and stabilizes TopBP1 by deubiquitination. Depletion of USP13 impedes ATR activation and hypersensitizes cells to replication stress-inducing agents. Furthermore, high USP13 expression enhances the replication stress response, promotes cancer cell chemoresistance, and is correlated with poor prognosis of cancer patients. Overall, these findings suggest that USP13 is a novel deubiquitinating enzyme for TopBP1 and coordinates the replication stress response.

SUBMITTER: Kim W

PROVIDER: S-EPMC7951086 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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USP13 regulates the replication stress response by deubiquitinating TopBP1.

Kim Wootae W Zhao Fei F Gao Huanyao H Qin Sisi S Hou Jing J Deng Min M Kloeber Jake A JA Huang Jinzhou J Zhou Qin Q Guo Guijie G Gao Ming M Zeng Xiangyu X Zhu Shouhai S Tu Xinyi X Wu Zheming Z Zhang Yong Y Yin Ping P Kaufmann Scott H SH Luo Kuntian K Lou Zhenkun Z

DNA repair 20210206

The DNA replication stress-induced checkpoint activated through the TopBP1-ATR axis is important for maintaining genomic stability. However, the regulation of TopBP1 in DNA-damage responses remains unclear. In this study, we identify the deubiquitinating enzyme (DUB) USP13 as an important regulator of TopBP1. Mechanistically, USP13 binds to TopBP1 and stabilizes TopBP1 by deubiquitination. Depletion of USP13 impedes ATR activation and hypersensitizes cells to replication stress-inducing agents. ...[more]

PMID: 33592542

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