Practice question

Silencing of spindle assembly checkpoint once all chromosomes achieve correct bi-orientation requires active disassembly of mitotic checkpoint complex and removal of checkpoint proteins from attached kinetochores. Central regulator is p31comet, also called MAD2L1BP, adaptor that binds closed conformation of Mad2 within MCC and recruits ATPase TRIP13 (Pch2 in yeast). TRIP13 uses ATP hydrolysis to convert closed Mad2 back to open inactive form, promoting disassociation of BubR1-Bub3-Cdc20 complex and freeing Cdc20 to activate APC/C. p31comet also competes with Mad1 for Mad2 binding, preventing new MCC generation and promoting stripping of Mad2 from kinetochores via dynein-mediated transport along microtubules. Overexpression of p31comet overrides checkpoint, causing premature anaphase even in presence of unattached chromosomes, while depletion prolongs mitotic arrest. Mps1 kinase, Mad1-Mad2 template, and Bub3-BubR1 instead propagate wait signal; they do not extinguish it. Thus p31comet-TRIP13 module serves as dedicated silencing machinery ensuring timely transition from checkpoint-on to checkpoint-off state, coupling attachment status to APC/C activation and mitotic progression.