Scholarlink

<p>Safeguarding chromosome ends against fusions via nonhomologous end joining (NHEJ) is essential for genome integrity. Paradoxically, the conserved NHEJ core factor Ku binds telomere ends. How it is prevented from promoting NHEJ remains unclear, as does the mechanism that allows Ku to coexist with telomere-protective DNA binding proteins, Rap1 in <i>Saccharomyces cerevisiae</i>. Here, we find that Rap1 directly inhibits Ku’s NHEJ function at telomeres. A single Rap1 molecule near a double-stand break suppresses NHEJ without displacing Ku in cells. Furthermore, Rap1 and Ku form a complex on short DNA duplexes in vitro. Cryo-EM shows Rap1 blocks Ku’s inward translocation on DNA – an essential step for NHEJ at DSBs. Nanopore sequencing of telomere fusions confirms this mechanism protects native telomere ends. These findings uncover a telomere protection mechanism where Rap1 restricts Ku’s inward translocation. This switches Ku from a repair-promoting to a protective role preventing NHEJ at telomeres.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Restriction of Ku translocation protects telomere ends

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月24日

查看全文
  • Stefano Mattarocci,
  • Sonia Baconnais,
  • Florian Roisné-Hamelin,
  • Sabrina Pobiega,
  • Olivier Alibert,
  • Vincent Morin,
  • Alice Deshayes,
  • Xavier Veaute,
  • Virginie Ropars,
  • Maelenn Chevreuil,
  • Johannes Mehringer,
  • Didier Busso,
  • Gerard Mazon,
  • Paloma Fernandez Varela,
  • Éric Le Cam,
  • Jean-Baptiste Charbonnier,
  • Philippe Cuniasse,
  • Stéphane Marcand

摘要

Safeguarding chromosome ends against fusions via nonhomologous end joining (NHEJ) is essential for genome integrity. Paradoxically, the conserved NHEJ core factor Ku binds telomere ends. How it is prevented from promoting NHEJ remains unclear, as does the mechanism that allows Ku to coexist with telomere-protective DNA binding proteins, Rap1 in Saccharomyces cerevisiae. Here, we find that Rap1 directly inhibits Ku’s NHEJ function at telomeres. A single Rap1 molecule near a double-stand break suppresses NHEJ without displacing Ku in cells. Furthermore, Rap1 and Ku form a complex on short DNA duplexes in vitro. Cryo-EM shows Rap1 blocks Ku’s inward translocation on DNA – an essential step for NHEJ at DSBs. Nanopore sequencing of telomere fusions confirms this mechanism protects native telomere ends. These findings uncover a telomere protection mechanism where Rap1 restricts Ku’s inward translocation. This switches Ku from a repair-promoting to a protective role preventing NHEJ at telomeres.