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<p>The nuclear envelope is a protective barrier for the genome and a mechanotransduction interface between cytoplasm and nucleus, whose malfunction disrupts nucleocytoplasmic transport, compromises DNA repair, accelerates telomere shortening, and promotes genomic instability. Mechanisms governing nuclear envelope remodeling and maintenance in interphase and post-mitotic cells remain poorly understood. Here, we report a role for dynamins, a family of essential brain-enriched membrane- and microtubule-binding GTPases, in preserving nuclear envelope and genomic homeostasis. Cells lacking dynamins exhibit nuclear envelope dysmorphisms, including buds with long narrow necks where damaged DNA frequently accumulates. These cells also show impaired autophagic clearance, reduced levels of key DNA repair proteins, and aberrant microtubules. Nocodazole treatment restores nuclear morphology and reduces DNA damage. Collectively, the data reveal that dynamins promote nuclear envelope homeostasis and removal of damaged DNA via their GTPase activity and interaction with microtubules, providing insights into mechanisms that uphold genome stability and counteract aging-related pathologies.</p>

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Dynamins maintain nuclear envelope homeostasis and genome stability

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月8日

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  • Célia Aveleira,
  • Thibaud Martial,
  • Loïc Carrique,
  • Rita Gaspar,
  • Ana Caulino-Rocha,
  • Izaak Myatt,
  • Franz Wendler,
  • Pauline Lascaux,
  • Misha Le Claire,
  • James Bancroft,
  • Carl Smythe,
  • Kristijan Ramadan,
  • Nuno Raimundo,
  • Ira Milosevic

摘要

The nuclear envelope is a protective barrier for the genome and a mechanotransduction interface between cytoplasm and nucleus, whose malfunction disrupts nucleocytoplasmic transport, compromises DNA repair, accelerates telomere shortening, and promotes genomic instability. Mechanisms governing nuclear envelope remodeling and maintenance in interphase and post-mitotic cells remain poorly understood. Here, we report a role for dynamins, a family of essential brain-enriched membrane- and microtubule-binding GTPases, in preserving nuclear envelope and genomic homeostasis. Cells lacking dynamins exhibit nuclear envelope dysmorphisms, including buds with long narrow necks where damaged DNA frequently accumulates. These cells also show impaired autophagic clearance, reduced levels of key DNA repair proteins, and aberrant microtubules. Nocodazole treatment restores nuclear morphology and reduces DNA damage. Collectively, the data reveal that dynamins promote nuclear envelope homeostasis and removal of damaged DNA via their GTPase activity and interaction with microtubules, providing insights into mechanisms that uphold genome stability and counteract aging-related pathologies.