Molecular Mechanisms of Spindle Assembly Checkpoint Activation and Silencing

In eukaryotic cell division, the Spindle Assembly Checkpoint (SAC) plays a key regulatory role by monitoring the status of chromosome-microtubule attachments and allowing chromosome segregation only after all chromosomes are properly attached to spindle microtubules. While the identities of SAC components have been known, in some cases, for over two decades, the molecular mechanisms of the SAC have remained mostly mysterious until very recently. In the past few years, advances in biochemical reconstitution, structural biology, and bioinformatics have fueled an explosion in the molecular understanding of the SAC. This chapter seeks to synthesize these recent advances and place them in a biological context, in order to explain the mechanisms of SAC activation and silencing at a molecular level.