气候变化领域集成服务门户(CCPortal): ATM controls the extent of DNA end resection by eliciting sequential posttranslational modifications of CtIP

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DOI	10.1073/pnas.2022600118
	ATM controls the extent of DNA end resection by eliciting sequential posttranslational modifications of CtIP
	Han J.; Wan L.; Jiang G.; Cao L.; Xia F.; Tian T.; Zhu X.; Wu M.; Huen M.S.Y.; Wang Y.; Liu T.; Huang J.
发表日期	2021
ISSN	00278424
卷号	118 期号:12
英文摘要	DNA end resection is a critical step in the repair of DNA double-strand breaks (DSBs) via homologous recombination (HR). However, the mechanisms governing the extent of resection at DSB sites undergoing homology-directed repair remain unclear. Here, we show that, upon DSB induction, the key resection factor CtIP is modified by the ubiquitin-like protein SUMO at lysine 578 in a PIAS4-dependent manner. CtIP SUMOylation occurs on damaged chromatin and requires prior hyperphosphorylation by the ATM protein kinase. SUMO-modified hyperphosphorylated CtIP is targeted by the SUMO-dependent E3 ubiquitin ligase RNF4 for polyubiquitination and subsequent degradation. Consequently, disruption of CtIP SUMOylation results in aberrant accumulation of CtIP at DSBs, which, in turn, causes uncontrolled excessive resection, defective HR, and increased cellular sensitivity to DSB-inducing agents. These findings reveal a previously unidentified regulatory mechanism that regulates CtIP activity at DSBs and thus the extent of end resection via ATM-dependent sequential posttranslational modification of CtIP. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	DNA end resection \| homologous recombination \| CtIP \| ATM \| hyperphosphorylation
语种	英语
scopus关键词	ATM protein; CtIP protein; double stranded DNA; lysine; PIAS4 protein; RNF4 protein; SUMO protein; ubiquitin protein ligase E3; unclassified drug; Article; cell function; cellular sensitivity; chromatin; controlled study; DNA end joining repair; DNA strand breakage; enzyme activity; homologous recombination; human; human cell; hyperphosphorylation; in vitro study; in vivo study; nuclear localization signal; polyubiquitination; priority journal; protein degradation; protein phosphorylation; protein processing; protein targeting; regulatory mechanism; sumoylation; ubiquitination
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180128
作者单位	MOE Key Laboratory of Biosystems Homeostasis & Protection, Life Sciences Institute, Zhejiang University, Hangzhou, 310058, China; Cancer Center, Zhejiang University, Hangzhou, 310058, China; Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China; Department of Cell Biology, Zhejiang University School of Medicine, Hangzhou, 310058, China; Department of Anatomy, University of Hong Kong, Hong Kong, Hong Kong; Center for Cancer Research, University of Hong Kong, Hong Kong, Hong Kong; Department of Chinese Medicine Science & Engineering, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058, China; Mechanisms of Transcription Laboratory, Francis Crick Institute, London, NW1 1AT, United Kingdom
推荐引用方式 GB/T 7714	Han J.,Wan L.,Jiang G.,et al. ATM controls the extent of DNA end resection by eliciting sequential posttranslational modifications of CtIP[J],2021,118(12).
APA	Han J..,Wan L..,Jiang G..,Cao L..,Xia F..,...&Huang J..(2021).ATM controls the extent of DNA end resection by eliciting sequential posttranslational modifications of CtIP.Proceedings of the National Academy of Sciences of the United States of America,118(12).
MLA	Han J.,et al."ATM controls the extent of DNA end resection by eliciting sequential posttranslational modifications of CtIP".Proceedings of the National Academy of Sciences of the United States of America 118.12(2021).