APC/C substrate degradation timing in yeast and mammalian cells. (A) Summary of the regulatory events leading to the metaphase–anaphase transition in yeast and mammalian cells, and the mechanisms that determine the timing and order of APC/C^Cdc20 substrate degradation in wild-type cells. (B) In yeast, defects in SAC function cause earlier Clb5 destruction but do not affect the timing of securin destruction. In contrast, in mammalian cells, SAC defects result in earlier cyclin A and securin destruction and anaphase onset. (C) In a prolonged SAC arrest, securin is stable, whereas Cks1 and the ABBA motif promote slow degradation of Clb5 and cyclin A. The diagrams in this figure are based on the current work and many previous studies (J. Pines, personal communication; Clute and Pines, 1999; den Elzen and Pines, 2001; Geley et al., 2001; Hagting et al., 2002; Wolthuis et al., 2008; Di Fiore and Pines, 2010; Shindo et al., 2012; Yaakov et al., 2012; Collin et al., 2013; Dick and Gerlich, 2013).