Practice question

Transition into anaphase is driven by activation of anaphase promoting complex cyclosome bound to Cdc20, a large 1.2 MDa cullin-RING E3 ubiquitin ligase. When SAC is satisfied, MCC disassembly through p31comet and TRIP13 releases Cdc20 permitting association with APC/C core. Active APC/C-Cdc20 recognizes destruction box degrons on two pivotal substrates: securin and Cyclin B. Polyubiquitination of securin triggers rapid proteolysis via 26S proteasome, discharging separase cysteine protease previously held inactive as pseudosubstrate. Free separase cleaves Scc1 or Rad21 kleisin subunit of cohesin rings at conserved E-x-x-R- site, opening tripartite ring and dissolving sister chromatid cohesion at centromeres remaining after Wapl-mediated arm removal. Simultaneously, cyclin B ubiquitination and degradation reduces CDK1 activity, permitting phosphatases PP1 and PP2A-B55 to dephosphorylate mitotic substrates, soften cortex and allow anaphase A chromatid-to-pole movement and anaphase B spindle elongation driven by Eg5 kinesin and cortical dynein. APC/C activation therefore couples cohesion destruction to mitotic exit preparation ensuring ordered segregation and genome stability. 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.