期刊
DNA REPAIR
卷 100, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.dnarep.2021.103063
关键词
USP13; TopBP1; Replication; DNA damage
This study identifies the deubiquitinating enzyme USP13 as a key regulator of TopBP1, stabilizing it and coordinating the replication stress response. High expression of USP13 enhances cancer cell chemoresistance and correlates with poor prognosis in cancer patients.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据