气候变化领域集成服务门户(CCPortal): The Srs2 helicase dampens DNA damage checkpoint by recycling RPA from chromatin

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DOI	10.1073/pnas.2020185118
	The Srs2 helicase dampens DNA damage checkpoint by recycling RPA from chromatin
	Dhingra N.; Kuppa S.; Wei L.; Pokhrel N.; Baburyan S.; Meng X.; Antony E.; Zhao X.
发表日期	2021
ISSN	00278424
卷号	118 期号:8
英文摘要	The DNA damage checkpoint induces many cellular changes to cope with genotoxic stress. However, persistent checkpoint signaling can be detrimental to growth partly due to blockage of cell cycle resumption. Checkpoint dampening is essential to counter such harmful effects, but its mechanisms remain to be understood. Here, we show that the DNA helicase Srs2 removes a key checkpoint sensor complex, RPA, from chromatin to down-regulate checkpoint signaling in budding yeast. The Srs2 and RPA antagonism is supported by their numerous suppressive genetic interactions. Importantly, moderate reduction of RPA binding to single-strand DNA (ssDNA) rescues hypercheckpoint signaling caused by the loss of Srs2 or its helicase activity. This rescue correlates with a reduction in the accumulated RPA and the associated checkpoint kinase on chromatin in srs2 mutants. Moreover, our data suggest that Srs2 regulation of RPA is separable from its roles in recombinational repair and critically contributes to genotoxin resistance. We conclude that dampening checkpoint by Srs2-mediated RPA recycling from chromatin aids cellular survival of genotoxic stress and has potential implications in other types of DNA transactions. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Checkpoint dampening; Genotoxic stress; Recombinational repair; RPA regulation; Srs2
语种	英语
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/180572
作者单位	Molecular Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, United States; Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO 63104, United States; Department of Biological Sciences, Marquette University, Milwaukee, WI 53201, United States; Department of Biological Sciences, City University of New York Hunter College, New York, NY 10065, United States
推荐引用方式 GB/T 7714	Dhingra N.,Kuppa S.,Wei L.,et al. The Srs2 helicase dampens DNA damage checkpoint by recycling RPA from chromatin[J],2021,118(8).
APA	Dhingra N..,Kuppa S..,Wei L..,Pokhrel N..,Baburyan S..,...&Zhao X..(2021).The Srs2 helicase dampens DNA damage checkpoint by recycling RPA from chromatin.Proceedings of the National Academy of Sciences of the United States of America,118(8).
MLA	Dhingra N.,et al."The Srs2 helicase dampens DNA damage checkpoint by recycling RPA from chromatin".Proceedings of the National Academy of Sciences of the United States of America 118.8(2021).