APC15 drives the turnover of MCC-CDC20 to make the spindle assembly checkpoint responsive to kinetoc

Abstract

Faithful chromosome segregation during mitosis depends on the spindle assembly checkpoint (SAC), which monitors kinetochore attachment to the mitotic spindle. Unattached kinetochores generate mitotic checkpoint proteins complexes (MCCs) that bind and inhibit the anaphase-promoting complex, or cyclosome (APC/C). How the SAC proficiently inhibits the APC/C but still allows its rapid activation when the last kinetochore attaches to the spindle is important for the understanding of how cells maintain genomic stability. We show that the APC/C subunit APC15 is required for the turnover of the APC/C co-activator CDC20 and release of MCCs during SAC signalling but not for APC/C activity per se. In the absence of APC15, MCCs and ubiquitylated CDC20 remain ‘locked’ onto the APC/C, which prevents the ubiquitylation and degradation of cyclin B1 when the SAC is satisfied. We conclude that APC15 mediates the constant turnover of CDC20 and MCCs on the APC/C to allow the SAC to respond to the attachment state of kinetochores. The spindle assembly checkpoint halts cell-cycle progression in the presence of unattached kinetochores by preventing activation of APC/C. Pines and colleagues find that APC15 has a critical role in regulating APC/C activation by promoting release of the inhibitory MCC complex from APC/C once the spindle assembly checkpoint is satisfied.

Cite this article

Mansfeld, J., Collin, P., Collins, M. et al. APC15 drives the turnover of MCC-CDC20 to make the spindle assembly checkpoint responsive to kinetochore attachment. Nat Cell Biol 13, 1234–1243 (2011). https://doi.org/10.1038/ncb2347

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