Practice question

Correct chromatid partitioning during anaphase integrates mechanical forces and biochemical resetting pathways. Physical separation depends on earlier APC/C-Cdc20 mediated securin degradation freeing separase to cleave cohesin subunit Scc1 at centromeres, allowing kinetochore microtubules to pull sister chromatids poleward via depolymerization coupled movement. However exit from high CDK state also essential. In budding yeast model, mitotic exit network monitors spindle elongation, activating Tem1 GTPase when daughter pole enters bud overcoming checkpoint inhibition by Kin4-Bub2-Bfa1 GAP complex. Tem1 triggers Cdc15 and Dbf2-Mob1 kinases leading to release of Cdc14 phosphatase from nucleolus. Cdc14 dephosphorylates CDK substrates including Cdh1 activating APC/C-Cdh1 for cyclin B and securin clearance plus spindle disassembly factors Ase1 and Fin1, Sic1 inhibitor synthesis via Swi5, and central spindle stabilization. Rising PP2A-B55 activity in mammals dephosphorylates PRC1 and ECT2 essential for central spindle bundling and RhoA activation for cytokinesis. Thus accurate segregation requires both cohesin removal and Cdc14 dependent phosphatase activation promoting low CDK environment enabling decondensation and division completion. 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.