Report

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

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Science  13 Apr 2012:
Vol. 336, Issue 6078, pp. 220-225
DOI: 10.1126/science.1217180

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To Cut or Not to Cut

During animal cell division, the final separation of daughter cells requires ESCRT-III (endosomal sorting complex required for transport III), the core membrane scission machinery. Carlton et al. (p. 220, published online 15 March; see the Perspective by Petronczki and Uhlmann) report that ESCRT-III modulates abscission timing through one of its subunits, CHMP4C. Depletion of CHMP4C results in faster resolution of the midbody, the cytoplasmic bridge that connects the daughter cells at the end of cytokinesis. This phenotype correlates with a differential spatiotemporal distribution of CHMP4C at the midbody. As CHMP4C is essential for activating the Aurora B–mediated abscission checkpoint, consequently, depletion of CHMP4C results in the accumulation of genetic damage. Thus, the ESCRT machinery protects the cell against genetic damage by coordinating its cytokinetic activity with the abscission checkpoint.

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.

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