Practice question

Mitotic Exit Network enables yeast cells to coordinate chromosome segregation completion with cytokinesis induction, preventing division before genome partitioned. The network is G-protein coupled kinase cascade anchored at spindle pole bodies. GTPase Tem1, kept inactive when spindle misaligned by Kin4-mediated phosphorylation of Bfa1-Bub2 GAP complex, becomes activated as daughter spindle pole body enters bud containing activating factor Lte1, a guanine nucleotide exchange factor like protein that antagonizes Bub2-Bfa1 hydrolysis activity. GTP-bound Tem1 recruits and activates Cdc15 kinase via scaffold Nud1, Cdc15 then phosphorylates and activates Dbf2-Mob1 LATS-like kinase complex. Dbf2-Mob1 phosphorylates Cfi1/Net1 inhibitor of Cdc14 as well as Cdc14 itself on nuclear localization signals, promoting dissociation from nucleolus and export to cytoplasm. Free Cdc14 dephosphorylates Cdh1 activating APC/C-Cdh1 for mitotic cyclin destruction, Swi5 enabling Sic1 transcription blocking CDK1, and other cytokinesis regulators. Result extinguishes CDK1 activity driving spindle disassembly, actin ring contraction and septum synthesis, finalizing division with appropriate genome segregation. 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.