Practice question

Anaphase-promoting complex bound to coactivator Cdc20 represents irreversible executor of metaphase exit, targeting securin and cyclin B. Inhibition of this ligase through multiple mechanisms arrests cells before chromosome separation. Endogenous inhibition occurs during spindle checkpoint activation where Mitotic Checkpoint Complex binds APC/C core blocking substrate recruitment. Exogenous inhibitors apcin occupying D-box binding pocket on Cdc20 and proTAME blocking APC/C activation, or depletion of Cdc20 protein itself, mimic checkpoint. Consequence is persistence of securin which continues to bind and suppress separase protease, and persistence of cyclin B maintaining high CDK1-phosphorylation of lamins, condensins and microtubule regulators. Cohesin rings at centromeres therefore remain intact, as separase cannot access Scc1 cleavage site, leaving sister chromatids interlinked despite bipolar spindle tension attempting to pull. Phenotypically cells display metaphase plate with fully aligned chromosomes but inability to initiate anaphase A movement. Prolonged arrest leads to mitotic slippage through slow cyclin B leakage, cohesion fatigue with partial separation, cell death or formation of tetraploid G1 cells after aberrant exit, illustrating essential role of APC/C-Cdc20 for timely anaphase.