Practice question

Finishing mitosis demands comprehensive reversal of CDK1 mediated phosphorylations and elimination of cyclin B activity. Cdc14 family phosphatases coordinate this program. In budding yeast, Cdc14 resides sequestered in nucleolus bound to inhibitor Net1 also called Cfi1. Mitotic entry maintains sequestration via high CDK activity. In early anaphase, FEAR pathway comprising separase, Slk19 homodimer, Spo12, Zds1 and Zds2 induces transient release. Subsequently Mitotic Exit Network MEN, Hippo-like cascade of Tem1 GTPase localized at daughter spindle pole body, polo kinase Cdc15 and Dbf2-Mob1 complex, fully liberates Cdc14 through phosphorylation of Net1. Free phosphatase preferentially dephosphorylates CDK sites containing serine-proline followed by lysine, including APC/C coactivator Cdh1 shifting APC/C activity from Cdc20 to Cdh1, transcription factor Swi5 enabling Sic1 CDK inhibitor synthesis, and S-phase regulator Cdc15 reinforcing feedback. Sic1 accumulation plus cyclin B degradation extinguishes CDK1 activity, allowing spindle disassembly, actomyosin ring contraction via Hof1 and Inn1 dephosphorylation, and septum formation. In mammals, orthologous CDC14A/B collaborate with PP2A-B55 for mitotic exit. 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.