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Science 336 (6078): 220-225

Copyright © 2012 by the American Association for the Advancement of Science

ESCRT-III Governs the Aurora B–Mediated Abscission Checkpoint Through CHMP4C

Jeremy G. Carlton,* Anna Caballe, Monica Agromayor, Magdalena Kloc, Juan Martin-Serrano{dagger}

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.

Department of Infectious Diseases, King’s College London School of Medicine, London SE1 9RT, UK.

* Present address: Division of Cancer Studies, King’s College London School of Medicine, London SE1 1UL, UK.

{dagger} To whom correspondence should be addressed. E-mail: juan.martin_serrano{at}kcl.ac.uk


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