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<p>In the presence of chromatin bridges in cytokinesis, human cells retain actin-rich structures (actin patches) at the base of the intercellular canal to prevent chromosome breakage. Here, we show that daughter nuclei connected by chromatin bridges are under mechanical tension that requires interaction of the nuclear membrane Sun1/2-Nesprin-2 Linker of Nucleoskeleton and Cytoskeleton (LINC) complex with the actin cytoskeleton, and an intact nuclear lamina. This nuclear tension promotes accumulation of Sun1/2-Nesprin-2 proteins at the base of chromatin bridges and local enrichment of the RhoA-activator PDZ RhoGEF through PDZ-binding to cytoplasmic Nesprin-2 spectrin repeats. In turn, PDZ RhoGEF activates the small GTPase RhoA and downstream ROCK-LIMK-Cofilin and mDia1 signaling to generate actin patches and prevent chromatin bridge breakage in cytokinesis. These findings identify a novel mechanosensing mechanism by which chromatin bridges promote remodeling of the actin cytoskeleton, through tension-induced activation of LINC-PDZ RhoGEF-RhoA signaling, to generate actin patches to preserve genome integrity.</p>

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Tension-sensitive LINC-RhoA signaling prevents chromatin bridge breakage in cytokinesis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月9日

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  • Sofia Balafouti,
  • Maria Kabouraki,
  • George Zachos,
  • Eleni Petsalaki

摘要

In the presence of chromatin bridges in cytokinesis, human cells retain actin-rich structures (actin patches) at the base of the intercellular canal to prevent chromosome breakage. Here, we show that daughter nuclei connected by chromatin bridges are under mechanical tension that requires interaction of the nuclear membrane Sun1/2-Nesprin-2 Linker of Nucleoskeleton and Cytoskeleton (LINC) complex with the actin cytoskeleton, and an intact nuclear lamina. This nuclear tension promotes accumulation of Sun1/2-Nesprin-2 proteins at the base of chromatin bridges and local enrichment of the RhoA-activator PDZ RhoGEF through PDZ-binding to cytoplasmic Nesprin-2 spectrin repeats. In turn, PDZ RhoGEF activates the small GTPase RhoA and downstream ROCK-LIMK-Cofilin and mDia1 signaling to generate actin patches and prevent chromatin bridge breakage in cytokinesis. These findings identify a novel mechanosensing mechanism by which chromatin bridges promote remodeling of the actin cytoskeleton, through tension-induced activation of LINC-PDZ RhoGEF-RhoA signaling, to generate actin patches to preserve genome integrity.