Practice question

The metaphase to anaphase transition is irreversible decision point governed by ubiquitin dependent proteolysis. When every chromosome achieves amphitelic kinetochore-microtubule attachment generating inter-kinetochore tension, spindle assembly checkpoint signaling through MCC production ceases. Dynein-mediated stripping of Mad1-Mad2 from kinetochores and p31comet-TRIP13 catalyzed MCC disassembly liberate coactivator Cdc20, enabling APC/C-Cdc20 ligase activation. Active APC/C polyubiquitinates securin via destruction box motif and cyclin B via D-box for rapid degradation by 26S proteasome. Securin degradation frees separase cysteine protease previously held as pseudosubstrate, while cyclin B destruction reduces CDK1 activity permitting dephosphorylation of mitotic substrates by PP1 and PP2A-B55. Free separase cleaves kleisin subunit Scc1 or Rad21 of cohesin tetramer encircling sister chromatids at centromeres rescued from earlier Wapl-mediated arm removal by Shugoshin-PP2A protection. Opening of cohesin ring dissolves linkage, allowing poleward microtubule pulling forces to separate sisters. Chromatid movement manifests as anaphase A toward poles and anaphase B spindle elongation driven by Eg5 kinesin and cortical dynein. 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.