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DOI10.1073/pnas.2017497118
RPA-mediated recruitment of Bre1 couples histone H2B ubiquitination to DNA replication and repair
Liu G.; Yan J.; Wang X.; Chen J.; Wang X.; Dong Y.; Zhang S.; Gan X.; Huang J.; Chen X.
发表日期2021
ISSN00278424
卷号118期号:8
英文摘要The ubiquitin E3 ligase Bre1-mediated H2B monoubiquitination (H2Bub) is essential for proper DNA replication and repair in eukaryotes. Deficiency in H2Bub causes genome instability and cancer. How the Bre1–H2Bub pathway is evoked in response to DNA replication or repair remains unknown. Here, we identify that the single-stranded DNA (ssDNA) binding factor RPA acts as a key mediator that couples Bre1-mediated H2Bub to DNA replication and repair in yeast. We found that RPA interacts with Bre1 in vitro and in vivo, and this interaction is stimulated by ssDNA. This association ensures the recruitment of Bre1 to replication forks or DNA breaks but does not affect its E3 ligase activity. Disruption of the interaction abolishes the local enrichment of H2Bub, resulting in impaired DNA replication, response to replication stress, and repair by homologous recombination, accompanied by increased genome instability and DNA damage sensitivity. Notably, we found that RNF20, the human homolog of Bre1, interacts with RPA70 in a conserved mode. Thus, RPA functions as a master regulator for the spatial–temporal control of H2Bub chromatin landscape during DNA replication and recombination, extending the versatile roles of RPA in guarding genome stability. © 2021 National Academy of Sciences. All rights reserved.
英文关键词Bre1; DNA replication; H2B ubiquitination; Homologous recombination; RPA
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/180536
作者单位Hubei Key Laboratory of Cell Homeostasis, Department of Genetics, College of Life Sciences, Institute for Advanced Studies, Wuhan University, Wuhan, 430072, China; MOE Key Laboratory of Biosystems Homeostasis and Protection, Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, 310058, China
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GB/T 7714
Liu G.,Yan J.,Wang X.,et al. RPA-mediated recruitment of Bre1 couples histone H2B ubiquitination to DNA replication and repair[J],2021,118(8).
APA Liu G..,Yan J..,Wang X..,Chen J..,Wang X..,...&Chen X..(2021).RPA-mediated recruitment of Bre1 couples histone H2B ubiquitination to DNA replication and repair.Proceedings of the National Academy of Sciences of the United States of America,118(8).
MLA Liu G.,et al."RPA-mediated recruitment of Bre1 couples histone H2B ubiquitination to DNA replication and repair".Proceedings of the National Academy of Sciences of the United States of America 118.8(2021).
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