The major biological function of the APC is to initiate chromosome segregation in mitosis. In metaphase, before APC activation, the duplicated chromosomes, or sister chromatids, are aligned at the center of the mitotic spindle. The APC promotes the ubiquitination and proteasomal destruction of securin, thereby unleashing a protease, separase, that cleaves cohesin proteins holding the sister chromatids together. The chromatids separate and are then pulled apart by the mitotic spindle in anaphase. The APC also triggers destruction of cyclins, the activating subunits of the cyclin-dependent kinases (Cdks). As a result, Cdk activity drops in anaphase. The resulting dephosphorylation of Cdk substrates is required for normal anaphase spindle function and for the completion of mitosis. The APC has numerous additional substrates, not shown here, that contribute to the control of late mitotic events and govern entry into the following G1.