Continuous nuclear envelope surveillance is required for DNA double strand break repair

Abstract Precise double-strand break (DSB) repair is paramount for genome stability. Homologous recombination (HR) is preferred to repair DSBs when a nearby sister chromatid ensures an error-free template. In Saccharomyces cerevisiae, this preference extends into anaphase and telophase (late mitosis...

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Bibliographic Details
Main Authors: Sara Medina-Suárez, Félix Machín
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-025-08416-x
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Summary:Abstract Precise double-strand break (DSB) repair is paramount for genome stability. Homologous recombination (HR) is preferred to repair DSBs when a nearby sister chromatid ensures an error-free template. In Saccharomyces cerevisiae, this preference extends into anaphase and telophase (late mitosis; late-M) despite sister chromatids having been pulled apart. Previously, we identified the nuclear envelope (NE) protein Msc1 as important for late-M DSB repair. Here, we report that Msc1 faces the NE lumen, and its depletion leads to DSB-independent over-compartmentalization of the nucleus and nuclear pore complex (NPC) mislocation. These phenotypes are partly shared by the highly conserved NE healing complex ESCRT-III. Finally, we show that these abnormal NE phenotypes are found throughout the cell cycle and in the DSB-driven G2/M arrest. These findings highlight the essential role of NE homeostasis in DSB repair.
ISSN:2399-3642