title: ESCRT-III governs the Aurora B-mediated abscission checkpoint through CHMP4C.
abstract: The endosomal sorting complex required for transport (ESCRT) machinery plays an evolutionarily conserved role in cytokinetic abscission, the final step of cell division where daughter cells are physically separated. Here, we show that charged multivesicular body (MVB) protein 4C (CHMP4C), a human ESCRT-III subunit, is involved in abscission timing. This function correlated with its differential spatiotemporal distribution during late stages of cytokinesis. Accordingly, CHMP4C functioned in the Aurora B-dependent abscission checkpoint to prevent both premature resolution of intercellular chromosome bridges and accumulation of DNA damage. CHMP4C engaged the chromosomal passenger complex (CPC) via interaction with Borealin, which suggested a model whereby CHMP4C inhibits abscission upon phosphorylation by Aurora B. Thus, the ESCRT machinery may protect against genetic damage by coordinating midbody resolution with the abscission checkpoint.
authors.affiliation: Department of Infectious Diseases, King's College London School of Medicine, London, UK.
authors.forename: Jeremy G
authors.initials: JG
authors.lastname: Carlton
authors.forename: Anna
authors.initials: A
authors.lastname: Caballe
authors.forename: Monica
authors.initials: M
authors.lastname: Agromayor
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kloc
authors.forename: Juan
authors.initials: J
authors.lastname: Martin-Serrano
mesh_terms: D064107:Aurora Kinase B; D064127:Aurora Kinases; D059447:Cell Cycle Checkpoints; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D002877:Chromosomes, Human / Q000378:metabolism; D048749:Cytokinesis; D004249:DNA Damage; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism; D006367:HeLa Cells; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D008938:Mitosis; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism
chemical_list: C490157:CDCA8 protein, human; C478397:CHMP4B protein, human; C541008:CHMP4C protein, human; D018797:Cell Cycle Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D015395:Histocompatibility Antigens Class I; D011993:Recombinant Fusion Proteins; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases