Exit from mitosis in budding yeast: Biphasic inactivation of the Cdc28-Clb2 mitotic kinase and the role of Cdc20

Cdc20, an activator of the anaphase-promoting complex (APC), is also requir ed for the exit from mitosis in Saccharomyces cerevisiae. Here we show that during mitosis, both the inactivation of Cdc28-Clb2 kinase and the degrada tion of mitotic cyclin Clb2 occur in two steps. The first phase of Clb2 pro teolysis, which commences at the metaphase-to-anaphase transition when Clb2 abundance is high, is dependent on Cdc20. The second wave of Clb2 destruct ion in telophase requires activation of the Cdc20 homolog, Hct1/Cdh1. The f irst phase of Clb2 destruction, which lowers the Cdc28-Clb2 kinase activity , is a prerequisite for the second. Thus, Clb2 proteolysis is not solely me diated by Hct1 as generally believed; instead, it requires a sequential act ion of both Cdc20 and Hct1.