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DOI10.1073/pnas.2106393118
Rtt105 promotes high-fidelity DNA replication and repair by regulating the single-stranded DNA-binding factor RPA
Wang X.; Dong Y.; Zhao X.; Li J.; Lee J.; Yan Z.; Yang S.; Wu W.; Hou X.; Liu G.; Zhang Y.; Song L.; Cai G.; Li Q.; Ira G.; Zhang X.; Chen X.
发表日期2021
ISSN0027-8424
卷号118期号:25
英文摘要Single-stranded DNA (ssDNA) covered with the heterotrimeric Replication Protein A (RPA) complex is a central intermediate of DNA replication and repair. How RPA is regulated to ensure the fidelity of DNA replication and repair remains poorly understood. Yeast Rtt105 is an RPA-interacting protein required for RPA nuclear import and efficient ssDNA binding. Here, we describe an important role of Rtt105 in high-fidelity DNA replication and recombination and demonstrate that these functions of Rtt105 primarily depend on its regulation of RPA. The deletion of RTT105 causes elevated spontaneous DNA mutations with large duplications or deletions mediated by microhomologies. Rtt105 is recruited to DNA doublestranded break (DSB) ends where it promotes RPA assembly and homologous recombination repair by gene conversion or breakinduced replication. In contrast, Rtt105 attenuates DSB repair by the mutagenic single-strand annealing or alternative end joining pathway. Thus, Rtt105-mediated regulation of RPA promotes highfidelity replication and recombination while suppressing repair by deleterious pathways. Finally, we show that the human RPAinteracting protein hRIP-α, a putative functional homolog of Rtt105, also stimulates RPA assembly on ssDNA, suggesting the conservation of an Rtt105-mediated mechanism. © 2021 National Academy of Sciences. All rights reserved.
英文关键词Genome stability; Homologous recombination; Replication fidelity; RPA; Rtt105
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/238886
作者单位Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Frontier Science Centre for Immunology and Metabolism, Wuhan University, Wuhan, 320072, China; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, United States; State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China; Key Laboratory of Plant Stress Biology, State Key Laboratory of Cotton Biology, School of Life Sciences, Henan University, Kaifeng, 475001, China; College of Life Sciences, Northwest AandF University, Yangling, 712100, China; School of Life Sciences, University of Science and Technology of China, Hefei, 230027, China
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GB/T 7714
Wang X.,Dong Y.,Zhao X.,et al. Rtt105 promotes high-fidelity DNA replication and repair by regulating the single-stranded DNA-binding factor RPA[J],2021,118(25).
APA Wang X..,Dong Y..,Zhao X..,Li J..,Lee J..,...&Chen X..(2021).Rtt105 promotes high-fidelity DNA replication and repair by regulating the single-stranded DNA-binding factor RPA.Proceedings of the National Academy of Sciences of the United States of America,118(25).
MLA Wang X.,et al."Rtt105 promotes high-fidelity DNA replication and repair by regulating the single-stranded DNA-binding factor RPA".Proceedings of the National Academy of Sciences of the United States of America 118.25(2021).
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