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

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 mammalian cells during interphase, which allowed 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…

• HF
  Human Frontier Science Program
• AN
  Agence Nationale de la Recherche
• HE
  H2020 European Research Council

  Awards: 309848, 311205