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USP13 regulates the replication stress response by deubiquitinating TopBP1. | LitMetric

USP13 regulates the replication stress response by deubiquitinating TopBP1.

DNA Repair (Amst)

Department of Oncology, Mayo Clinic, Rochester, MN, 55905, USA; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, 55905, USA. Electronic address:

Published: April 2021

AI Article Synopsis

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7951086PMC
http://dx.doi.org/10.1016/j.dnarep.2021.103063DOI Listing

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