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

doi:10.1016/j.dnarep.2021.103063

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

Oncology

Research output: Contribution to journal › Article › peer-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 language	English (US)
Article number	103063
Journal	DNA Repair
Volume	100
DOIs	https://doi.org/10.1016/j.dnarep.2021.103063
State	Published - Apr 2021

Keywords

DNA damage
Replication
TopBP1
USP13

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Cell Biology

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10.1016/j.dnarep.2021.103063

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title = "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.",

keywords = "DNA damage, Replication, TopBP1, USP13",

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

note = "Publisher Copyright: {\textcopyright} 2021 Elsevier B.V.",

year = "2021",

month = apr,

doi = "10.1016/j.dnarep.2021.103063",

language = "English (US)",

volume = "100",

journal = "DNA Repair",

issn = "1568-7864",

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T1 - USP13 regulates the replication stress response by deubiquitinating TopBP1

AU - Kim, Wootae

AU - Zhao, Fei

AU - Gao, Huanyao

AU - Qin, Sisi

AU - Hou, Jing

AU - Deng, Min

AU - Kloeber, Jake A.

AU - Huang, Jinzhou

AU - Zhou, Qin

AU - Guo, Guijie

AU - Gao, Ming

AU - Zeng, Xiangyu

AU - Zhu, Shouhai

AU - Tu, Xinyi

AU - Wu, Zheming

AU - Zhang, Yong

AU - Yin, Ping

AU - Kaufmann, Scott H.

AU - Luo, Kuntian

AU - Lou, Zhenkun

PY - 2021/4

Y1 - 2021/4

N2 - 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.

AB - 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.

KW - DNA damage

KW - Replication

KW - TopBP1

KW - USP13

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DO - 10.1016/j.dnarep.2021.103063

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JO - DNA Repair

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ER -

USP13 regulates the replication stress response by deubiquitinating TopBP1

Abstract

Keywords

ASJC Scopus subject areas

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