title: ESCRT III repairs nuclear envelope ruptures during cell migration to limit DNA damage and cell death.
abstract: 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 depended on efficient nuclear envelope and DNA repair machineries. Nuclear envelope opening in migrating leukocytes could have potentially important consequences for normal and pathological immune responses.
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR 144, F-75005 Paris, France. Institut Pierre-Gilles de Gennes, PSL Research University, F-75005 Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Raab
authors.affiliation: Institut Curie, PSL Research University, INSERM, U 932, F-75005 Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Gentili
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR 144, F-75005 Paris, France.
authors.forename: H
authors.initials: H
authors.lastname: de Belly
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR 144, F-75005 Paris, France.
authors.forename: H R
authors.initials: HR
authors.lastname: Thiam
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR 144, F-75005 Paris, France. Institut Pierre-Gilles de Gennes, PSL Research University, F-75005 Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Vargas
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR 144, F-75005 Paris, France.
authors.forename: A J
authors.initials: AJ
authors.lastname: Jimenez
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR 144, F-75005 Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Lautenschlaeger
authors.affiliation: Laboratoire de Physique Théorique de la Matière Condensée, CNRS UMR 7600, Université Pierre et Marie Curie, Paris, France. Laboratoire Jean Perrin, CNRS UMR 8237, Université Pierre et Marie Curie, Paris, France.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Voituriez
authors.affiliation: Institut Curie, PSL Research University, INSERM, U 932, F-75005 Paris, France.
authors.forename: A M
authors.initials: AM
authors.lastname: Lennon-Duménil
authors.affiliation: Institut Curie, PSL Research University, INSERM, U 932, F-75005 Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Manel
authors.affiliation: Institut Curie, PSL Research University, CNRS, UMR 144, F-75005 Paris, France. Institut Pierre-Gilles de Gennes, PSL Research University, F-75005 Paris, France. matthieu.piel@curie.fr.
authors.forename: M
authors.initials: M
authors.lastname: Piel
mesh_terms: D000818:Animals; D016923:Cell Death; D002465:Cell Movement; D003593:Cytoplasm / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007109:Immunity / Q000235:genetics; D007399:Interphase; D007962:Leukocytes / Q000276:immunology / Q000648:ultrastructure; D051379:Mice; D009685:Nuclear Envelope / Q000648:ultrastructure*; D009687:Nuclear Proteins / Q000378:metabolism
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D009687:Nuclear Proteins