Practice question

Mitotic exit requires not only destruction of cyclin B but comprehensive reversal of CDK1-Cyclin B phosphorylation on hundreds of substrates. Specialized phosphatases execute this program. In budding yeast, Cdc14 is the master phosphatase. Most of the cell cycle it is sequestered in nucleolus bound to inhibitor Net1 or Cfi1. Two release pathways operate sequentially: the Cdc Fourteen Early Anaphase Release pathway involving separase, Slk19, Spo12 and Zds1/Zds2 provides transient liberation in early anaphase, while the Mitotic Exit Network composed of Tem1, Cdc15 and Dbf2-Mob1 kinases sustains release. Active Cdc14 preferentially dephosphorylates serine followed by proline with basic Lys in +3 position, matching CDK consensus, including targets Cdh1 converting APC/C coactivator from Cdc20 to Cdh1, Swi5 transcription factor enabling Sic1 inhibitor synthesis and Cdc15 reinforcing feedback. In mammals, CDC14A/B and PP2A-B55, regulated by Greatwall-ENSA pathway, fulfill analogous roles. Inhibition traps cells in late anaphase with segregated but condensed chromosomes unable to reform nuclei or undergo cytokinesis. Additional feedback loops involving polo-like kinases, phosphatases and SCF-mediated degradation reinforce irreversibility and protect against premature progression that would compromise genome integrity and viability.