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<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>

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Mechanisms and regulation of DNA end resection in the maintenance of genome stability

  • 期刊论文

  • 发表日期：

    2025年3月25日

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  • Raphael Ceccaldi,
  • Petr Cejka

摘要

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.