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DOI10.1073/pnas.2109334118
A mechanism for Rad53 to couple leading- And lagging-strand DNA synthesis under replication stress in budding yeast
Serra-Cardona A.; Yu C.; Zhang X.; Hua X.; Yao Y.; Zhou J.; Gan H.; Zhang Z.
发表日期2021
ISSN0027-8424
卷号118期号:38
英文摘要In response to DNA replication stress, DNA replication checkpoint kinase Mec1 phosphorylates Mrc1, which in turn activates Rad53 to prevent the generation of deleterious single-stranded DNA, a process that remains poorly understood. We previously reported that lagging-strand DNA synthesis proceeds farther than leading strand in rad53-1 mutant cells defective in replication checkpoint under replication stress, resulting in the exposure of long stretches of the leading-strand templates. Here, we show that asymmetric DNA synthesis is also observed in mec1-100 and mrc1-AQ cells defective in replication checkpoint but, surprisingly, not in mrc1Δ cells in which both DNA replication and checkpoint functions of Mrc1 are missing. Furthermore, depletion of either Mrc1 or its partner, Tof1, suppresses the asymmetric DNA synthesis in rad53-1 mutant cells. Thus, the DNA replication checkpoint pathway couples leading- and lagging-strand DNA synthesis by attenuating the replication function of Mrc1-Tof1 under replication stress. © 2021 National Academy of Sciences. All rights reserved.
英文关键词Asymmetric DNA synthesis; Deleterious ssDNA; Mrc1; Rad53; Replication stress
语种英语
scopus关键词ATR protein; checkpoint kinase 2; protein Mec1; protein Tof1; single stranded DNA; unclassified drug; Article; budding yeast; DNA damage checkpoint; DNA synthesis; enzyme mechanism; eukaryotic cell; gene repression; nonhuman; protein protein interaction; signal transduction
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/238795
作者单位Institute for Cancer Genetics, Columbia University Irving Medical Center, New York, NY 10032, United States; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, United States; Department of Pediatrics, Columbia University Medical Center, New York, NY 10032, United States; Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, United States; The Hormel Institute, University of Minnesota, Austin, MN 55912, United States; Department of Regenerative Medicine, School of Pharmaceutical Science, Jilin University, Changchun, 130021, China; Shenzhen Key Laboratory of Synthetic Genomics, Guangdong Provincial Key Laboratory of Synthetic Genomics, Chinese Academy of Sciences Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China
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Serra-Cardona A.,Yu C.,Zhang X.,et al. A mechanism for Rad53 to couple leading- And lagging-strand DNA synthesis under replication stress in budding yeast[J],2021,118(38).
APA Serra-Cardona A..,Yu C..,Zhang X..,Hua X..,Yao Y..,...&Zhang Z..(2021).A mechanism for Rad53 to couple leading- And lagging-strand DNA synthesis under replication stress in budding yeast.Proceedings of the National Academy of Sciences of the United States of America,118(38).
MLA Serra-Cardona A.,et al."A mechanism for Rad53 to couple leading- And lagging-strand DNA synthesis under replication stress in budding yeast".Proceedings of the National Academy of Sciences of the United States of America 118.38(2021).
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