{"title":"Mechanisms and regulation of DNA end resection in the maintenance of genome stability","authors":"Raphael Ceccaldi, Petr Cejka","doi":"10.1038/s41580-025-00841-4","DOIUrl":null,"url":null,"abstract":"<p>DNA end resection is a crucial early step in most DNA double-strand break (DSB) repair pathways. Resection involves the nucleolytic degradation of 5′ ends at DSB sites to generate 3′ single-stranded DNA overhangs. The first, short-range resection step is catalysed by the nuclease MRE11, acting as part of the MRE11–RAD50–NBS1 complex. Subsequent long-range resection is catalysed by the nucleases EXO1 and/or DNA2. Resected DNA is necessary for homology search and the priming of DNA synthesis in homologous recombination. DNA overhangs may also mediate DNA annealing in the microhomology-mediated end-joining and single-strand annealing pathways, and activate the DNA damage response. By contrast, DNA end resection inhibits DSB repair by non-homologous end-joining. In this Review, we discuss the importance of DNA end resection in various DSB repair pathways, the molecular mechanisms of end resection and its regulation, focusing on phosphorylation and other post-translational modifications that control resection throughout the cell cycle and in response to DNA damage.</p>","PeriodicalId":19051,"journal":{"name":"Nature Reviews Molecular Cell Biology","volume":"71 1","pages":""},"PeriodicalIF":81.3000,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Reviews Molecular Cell Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1038/s41580-025-00841-4","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
DNA end resection is a crucial early step in most DNA double-strand break (DSB) repair pathways. Resection involves the nucleolytic degradation of 5′ ends at DSB sites to generate 3′ single-stranded DNA overhangs. The first, short-range resection step is catalysed by the nuclease MRE11, acting as part of the MRE11–RAD50–NBS1 complex. Subsequent long-range resection is catalysed by the nucleases EXO1 and/or DNA2. Resected DNA is necessary for homology search and the priming of DNA synthesis in homologous recombination. DNA overhangs may also mediate DNA annealing in the microhomology-mediated end-joining and single-strand annealing pathways, and activate the DNA damage response. By contrast, DNA end resection inhibits DSB repair by non-homologous end-joining. In this Review, we discuss the importance of DNA end resection in various DSB repair pathways, the molecular mechanisms of end resection and its regulation, focusing on phosphorylation and other post-translational modifications that control resection throughout the cell cycle and in response to DNA damage.
期刊介绍:
Nature Reviews Molecular Cell Biology is a prestigious journal that aims to be the primary source of reviews and commentaries for the scientific communities it serves. The journal strives to publish articles that are authoritative, accessible, and enriched with easily understandable figures, tables, and other display items. The goal is to provide an unparalleled service to authors, referees, and readers, and the journal works diligently to maximize the usefulness and impact of each article. Nature Reviews Molecular Cell Biology publishes a variety of article types, including Reviews, Perspectives, Comments, and Research Highlights, all of which are relevant to molecular and cell biologists. The journal's broad scope ensures that the articles it publishes reach the widest possible audience.