Figure 1.

The mitotic checkpoint or SAC. SAC factors are activated when a signal is detected from unattached kinetochores to spindle microtubules. Active SAC inhibits CDC20. CDC20 is an essential regulator of cell division, which binds to and activates the APC/C. APC/C is a large complex of proteins with ubiquitin ligase activity. It triggers the transition from metaphase to anaphase by ubiquitylating cyclins (e.g., cyclin B1) and securin. Securin forms a complex with separase and thereby blocks separase activity. APC/C-mediated proteasomal degradation of securin liberates and activates separase. A second regulatory step of separase activity is its phosphorylation by CDK1. APC/C-mediated proteasomal degradation of cyclin B1 inactivates CDK1. Activated separase cleaves cohesin, resulting in the separation of sister chromatids and triggering the anaphase. Thus, inhibition of CDC20 and APC/C by SAC leads to a temporary pause of mitosis and continuation of the attachment of the sister chromatids (due to inactive separase enzyme) until all kinetochores are joined to the mitotic spindle [24].