ESCRT III repairs nuclear envelope ruptures during cell migration to limit DNA damage and cell death

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Science  24 Mar 2016:
DOI: 10.1126/science.aad7611

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In eukaryotic cells, the nuclear envelope separates the genomic DNA from the cytoplasmic space and regulates protein trafficking between the two compartments. This barrier is only transiently dissolved during mitosis. Here we found that it also opened at high frequency in migrating cells during interphase, allowing nuclear proteins to leak out and cytoplasmic proteins to leak in. This transient opening was caused by nuclear deformation and was rapidly repaired in an ESCRT (endosomal sorting complexes required for transport)-dependent manner. DNA double strand breaks coincided with nuclear envelope opening events. As a consequence, survival of cells migrating through confining environments depended on efficient nuclear envelope and DNA repair machineries. Nuclear envelope opening in migrating leukocytes could potentially have important consequences for normal and pathological immune responses.

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