Practice question

In budding yeast, mitotic exit is controlled by mitotic exit network, abbreviated MEN, culminating in release of phosphatase Cdc14 from nucleolus to dephosphorylate CDK substrates and activate APC/C-Cdh1 and Sic1 to drive G1 entry. Premature exit would cause cytokinesis before chromosome segregation, generating aneuploid progeny. Two mechanisms prevent this: inhibition of upstream GTPase Tem1 keeps MEN inactive until anaphase when Tem1 is recruited to spindle pole body and activated by Lte1, ensuring that only elongated spindles trigger exit. Separately, Cdh1, alternative activator of APC/C, is kept inactive during early mitosis by CDK1-dependent phosphorylation that prevents its binding to APC/C core, avoiding early degradation of mitotic cyclins Clb2 and polo kinase Cdc5. Phosphorylation also excludes Cdh1 from nucleus. Both restraints must be relieved: Tem1 activation drives Cdc14 release, leading to Cdh1 dephosphorylation and APC/C-Cdh1 activation that clears remaining cyclins. Loss of either brake causes premature Cdh1 activity and MEN firing, explaining why combined inhibition of Tem1 and phosphorylation of Cdh1 acts as dual safeguard against untimely mitotic exit and cytokinesis.