Practice question

Cells delay anaphase until accurate chromosome alignment ensures equal segregation. Spindle assembly checkpoint implements this surveillance. Core machinery localizes to unattached kinetochores where scaffold KNL1 phosphorylated at MELT repeats by Mps1 kinase recruits Bub3-Bub1 and Bub3-BubR1 complexes. Bub1 phosphorylates histone H2A and Mad1, promoting catalytic platform where open Mad2 converts to closed Mad2 capable of trapping Cdc20. Mad2, BubR1 and Bub3 associate with Cdc20 forming diffusible Mitotic Checkpoint Complex that inhibits APC/C-Cdc20 by inserting BubR1 pseudosubstrate KEN boxes into Cdc20 WD40 propeller and blocking APC/C catalytic core. As a result, degradable substrates securin and cyclin B remain stable, maintaining separase inhibition and high CDK1 activity to preserve mitotic state. Upon microtubule attachment, Mps1 removal, dynein-mediated stripping of Mad1-Mad2 toward poles and p31comet-TRIP13 catalyzed MCC disassembly terminate signaling. Cdc20 liberation activates APC/C, leading to securin cleavage enabling cohesin removal and chromosome separation, ensuring genome stability before mitotic exit and cytokinesis induction. 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.