Inhibiting the inhibitor: how the Spindle Assembly Checkpoint gets silenced

Abstract

To prevent chromosome mis-segregation, the Spindle Assembly Checkpoint causes a mitotic arrest in cells containing unattached kinetochores through inhibition of CDC20-dependent APC/C activation. The robustness of the checkpoint is illustrated by the fact that the occurrence of even one single unattached kinetochore is sufficient to induce a mitotic arrest. Intriguingly, the checkpoint is almost immediately inactivated after the attachment of the last kinetochore. In this review, the mechanisms for this checkpoint silencing are discussed.