APC(Cdc20) promotes exit from mitosis by destroying the anaphase inhibitorPds1 and cyclin Clb5

Ubiquitin-mediated proteolysis due to the anaphase-promoting complex/cyclos ome (APC/C) is essential for separation of sister chromatids, requiring deg radation of the anaphase inhibitor Pds1, and for exit from mitosis, requiri ng inactivation of cyclin B Cdk1 kinases(1). Exit from mitosis in yeast inv olves accumulation of the cyclin kinase inhibitor Sic1 as well as cyclin pr oteolysis mediated by APC/C bound by the activating subunit Cdh1/Hct1 (ApC( Cdh1))(2,3). Both processes require the Cdc(14) phosphatase, whose release from the nucleolus during anaphase causes dephosphorylation and thereby act ivation of Cdh1 and accumulation of another protein, Sic1 (refs 4-7). We do not know what determines the release of Cdc14 and enables it to promote Cd k1 inactivation, but it is known to be dependent on APC/C bound by Cdc20 (A pC(Cdc20)) (ref. 4). Here we show that ApC(Cdc20) allows activation of Cdc 14 and promotes exit from mitosis by mediating proteolysis of Pds1 and the S phase cyclin Clb5 in the yeast Saccharomyces cerevisiae. Degradation of P ds1 is necessary for release of Cdc14 from the nucleolus, whereas degradati on of Clb5 is crucial if Cdc14 is to overwhelm Cdk1 and activate its foes ( Cdh1 and Sic1). Remarkably, cells lacking both Pds1 and Clb5 can proliferat e in the complete absence of Cdc20.