Multiple mechanisms determine the order of APC/C substrate degradation in mitosis.
Bottom Line: The spindle assembly checkpoint delays the onset of Clb5 degradation but does not influence securin degradation.The degradation of securin and Dbf4 is delayed by Cdk1-dependent phosphorylation near their Cdc20-binding sites.Thus, a remarkably diverse array of mechanisms generates robust ordering of APC/C(Cdc20) substrate destruction.
Affiliation: Department of Physiology and Department of Biochemistry and Biophysics and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158.Show MeSH
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Mentions: Our results, together with those from previous single-cell studies, provide a detailed temporal picture of how yeast cells progress toward the metaphase–anaphase transition (Fig. 7). The process begins with inactivation of the SAC, which inhibits APC/CCdc20 activity until all sister chromatids are properly attached to the spindle. Activated APC/CCdc20 first degrades the S cyclin Clb5 with a mean half-life of 3.4 min. About 6 min later, securin is degraded with a mean half-life of 4.7 min. Soon after securin degradation begins, separase is abruptly activated, and only 1 min is required for separase to cleave enough cohesin to promote sister chromatid separation (Yaakov et al., 2012). By the time of sister chromatid separation, Clb5 is fully degraded but more than half of securin remains.
Affiliation: Department of Physiology and Department of Biochemistry and Biophysics and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158.