MutS recognition of mismatches within primed DNA replication intermediates

IF 3 3区生物学 Q2 GENETICS & HEREDITY

DNA Repair Pub Date : 2022-11-01 DOI:10.1016/j.dnarep.2022.103392

Milagros Inés Ibáñez Busseti , Lucía Malvina Margara , Sofía Daiana Castell , Marisa Mariel Fernández , Emilio Luis Malchiodi , Guillermo Gabriel Montich , Virginia Miguel , Carlos Enrique Argaraña , Mariela Roxana Monti

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引用次数: 0

Abstract

MutS initiates mismatch repair by recognizing mismatches in newly replicated DNA. Specific interactions between MutS and mismatches within double-stranded DNA promote ADP-ATP exchange and a conformational change into a sliding clamp. Here, we demonstrated that MutS from Pseudomonas aeruginosa associates with primed DNA replication intermediates. The predicted structure of this MutS-DNA complex revealed a new DNA binding site, in which Asn 279 and Arg 272 appeared to directly interact with the 3′-OH terminus of primed DNA. Mutation of these residues resulted in a noticeable defect in the interaction of MutS with primed DNA substrates. Remarkably, MutS interaction with a mismatch within primed DNA induced a compaction of the protein structure and impaired the formation of an ATP-bound sliding clamp. Our findings reveal a novel DNA binding mode, conformational change and intramolecular signaling for MutS recognition of mismatches within primed DNA structures.

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MutS对引物DNA复制中间体错配的识别

MutS通过识别新复制DNA中的错配来启动错配修复。mut之间的特定相互作用和双链DNA内的错配促进ADP-ATP交换和构象改变为滑动钳。在这里，我们证明来自铜绿假单胞菌的MutS与引物DNA复制中间体相关。该mts -DNA复合物的预测结构揭示了一个新的DNA结合位点，其中Asn 279和Arg 272似乎直接与引物DNA的3 ' -OH端相互作用。这些残基的突变导致MutS与引物DNA底物相互作用的明显缺陷。值得注意的是，MutS与引物DNA内的错配相互作用诱导了蛋白质结构的压实，并破坏了atp结合滑动钳的形成。我们的发现揭示了一种新的DNA结合模式、构象变化和分子内信号传导，用于MutS识别引物DNA结构中的错配。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

DNA Repair 生物-毒理学

CiteScore

7.60

自引率

5.30%

发文量

审稿时长

59 days

期刊介绍： DNA Repair provides a forum for the comprehensive coverage of DNA repair and cellular responses to DNA damage. The journal publishes original observations on genetic, cellular, biochemical, structural and molecular aspects of DNA repair, mutagenesis, cell cycle regulation, apoptosis and other biological responses in cells exposed to genomic insult, as well as their relationship to human disease. DNA Repair publishes full-length research articles, brief reports on research, and reviews. The journal welcomes articles describing databases, methods and new technologies supporting research on DNA repair and responses to DNA damage. Letters to the Editor, hot topics and classics in DNA repair, historical reflections, book reviews and meeting reports also will be considered for publication.