USP13 regulates the replication stress response by deubiquitinating TopBP1

Wootae Kim, Fei Zhao, Huanyao Gao, Sisi Qin, Jing Hou, Min Deng, Jake A. Kloeber, Jinzhou Huang, Qin Zhou, Guijie Guo, Ming Gao, Xiangyu Zeng, Shouhai Zhu, Xinyi Tu, Zheming Wu, Yong Zhang, Ping Yin, Scott H. Kaufmann, Kuntian Luo, Zhenkun Lou

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number103063
JournalDNA Repair
Volume100
DOIs
StatePublished - Apr 2021

Keywords

  • DNA damage
  • Replication
  • TopBP1
  • USP13

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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