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DOI10.1073/pnas.2016287118
A conserved Ctp1/CtIP C-terminal peptide stimulates Mre11 endonuclease activity
Zdravković A.; Daley J.M.; Dutta A.; Niwa T.; Murayama Y.; Kanamaru S.; Ito K.; Maki T.; Argunhan B.; Takahashi M.; Tsubouchi H.; Sung P.; Iwasaki H.
发表日期2021
ISSN00278424
卷号118期号:11
英文摘要The Mre11-Rad50-Nbs1 complex (MRN) is important for repairing DNA double-strand breaks (DSBs) by homologous recombination (HR). The endonuclease activity of MRN is critical for resecting 5′- ended DNA strands at DSB ends, producing 3′-ended single-strand DNA, a prerequisite for HR. This endonuclease activity is stimulated by Ctp1, the Schizosaccharomyces pombe homolog of human CtIP. Here, with purified proteins, we show that Ctp1 phosphorylation stimulatesMRN endonuclease activity by inducing the association of Ctp1 with Nbs1. The highly conserved extreme C terminus of Ctp1 is indispensable for MRN activation. Importantly, a polypeptide composed of the conserved 15 amino acids at the C terminus of Ctp1 (CT15) is sufficient to stimulate Mre11 endonuclease activity. Furthermore, the CT15 equivalent from CtIP can stimulate human MRE11 endonuclease activity, arguing for the generality of this stimulatory mechanism. Thus, we propose that Nbs1-mediated recruitment of CT15 plays a pivotal role in the activation of the Mre11 endonuclease by Ctp1/CtIP. © 2021 National Academy of Sciences. All rights reserved.
英文关键词Ctp1/CtIP; Double-strand break repair; Fission yeast; Homologous recombination; Mre11-Rad50-Nbs1
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/180241
作者单位School and Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Kanagawa, 226-8503, Japan; Institute of Innovative Research, Tokyo Institute of Technology, Kanagawa, 226-8503, Japan; Department of Biochemistry and Structural Biology, University of Texas Health Science Center, San Antonio, TX 78229, United States; Center for Frontier Research, National Institute of Genetics, Shizuoka, 411-8540, Japan
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Zdravković A.,Daley J.M.,Dutta A.,et al. A conserved Ctp1/CtIP C-terminal peptide stimulates Mre11 endonuclease activity[J],2021,118(11).
APA Zdravković A..,Daley J.M..,Dutta A..,Niwa T..,Murayama Y..,...&Iwasaki H..(2021).A conserved Ctp1/CtIP C-terminal peptide stimulates Mre11 endonuclease activity.Proceedings of the National Academy of Sciences of the United States of America,118(11).
MLA Zdravković A.,et al."A conserved Ctp1/CtIP C-terminal peptide stimulates Mre11 endonuclease activity".Proceedings of the National Academy of Sciences of the United States of America 118.11(2021).
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