The multilayer regulation of the metaphase-to-anaphase transition

The fluctuating activity of the cyclin-dependent kinases (Cdks) is critical for the periodic phosphorylation of a given Cdk substrate. Previous studies have been focus on the positive role of Cdk-dependent protein phosphorylation in cell cycle progression. Recent studies indicate that, in budding yeast, highly active S-phase cyclin-associated Cdk not only promotes DNA synthesis but also inhibits the initiation of chromosome segregation. The FEAR (Cdc14 early anaphase release) pathway alleviates the negative effect of the S-phase cyclin on anaphase by promoting the dephosphorylation of S-phase cyclin-specific substrates, revealing a new layer of regulation in the metaphase-to-anaphase transition.