| Literature DB >> 33592542 |
Wootae Kim1, Fei Zhao1, Huanyao Gao2, Sisi Qin3, Jing Hou1, Min Deng1, Jake A Kloeber4, Jinzhou Huang1, Qin Zhou1, Guijie Guo1, Ming Gao1, Xiangyu Zeng1, Shouhai Zhu1, Xinyi Tu1, Zheming Wu1, Yong Zhang1, Ping Yin1, Scott H Kaufmann2, Kuntian Luo1, Zhenkun Lou5.
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.Entities:
Keywords: DNA damage; Replication; TopBP1; USP13
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Year: 2021 PMID： 33592542 PMCID： PMC7951086 DOI： 10.1016/j.dnarep.2021.103063
Source DB: PubMed Journal: DNA Repair (Amst) ISSN： 1568-7856