FIGURE 19-25 Regulation of cohesin cleavage. Separase, a protease that can cleave the Scc1 subunit of cohesin complexes, is inhibited before anaphase by the binding of securin. Mitotic CDKs also inhibit separase by phosphorylating it. When all the kinetochores have attached to spindle microtubules and the spindle apparatus is properly assembled and oriented, the Cdc20 specificity factor associated with APC/C directs it to ubiquitinylate securin and mitotic cyclins. Following securin degradation and a decrease in mitotic CDK activity, the released and dephosphorylated separase cleaves the Scc1 subunit, breaking the cohesin circles and allowing sister chromatids to be pulled apart by the spindle apparatus that is pulling them toward opposite spindle poles.