Dynamins maintain nuclear envelope homeostasis and genome stability

Jan 8, 2026Nature communications

Dynamins help keep the nuclear envelope stable and protect the genome

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Abstract

Dynamins are essential for maintaining nuclear envelope integrity and genomic stability.

Cells without dynamins display abnormal nuclear envelope shapes and accumulate damaged DNA.
Impaired cellular processes include reduced autophagic clearance and lower levels of important DNA repair proteins.
Abnormalities in microtubule structures are observed in dynamin-deficient cells.
Treatment with nocodazole can correct nuclear shape and decrease DNA damage.
Dynamins may influence nuclear envelope stability and the removal of damaged DNA through their activity and interaction with microtubules.

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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.

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Dynamins maintain nuclear envelope homeostasis and genome stability

Abstract

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