Practice question

Metaphase to anaphase transition represents irreversible commitment executed by APC/C bound to Cdc20 coactivator. Throughout prometaphase chromosomes attach via kinetochores, generating unattached kinetochore signal converting Mad2 to active inhibitor forming mitotic checkpoint complex with BubR1, Bub3, and Cdc20 that binds APC/C core to block E2 recruitment. Upon achievement of biorientation of all chromosomes and establishment of tension, checkpoint protein recruitment stops, complex disassembles, and free Cdc20 associates with phosphorylated APC/C previously primed by CDK1 and Plk1. Active APC/C-Cdc20 polyubiquitinates securin and cyclin B with K11 chains for proteasomal destruction. Securin normally binds and locks separase protease in inactive conformation together with cyclin B-CDK1 phosphorylation. Degradation liberates separase that cleaves kleisin Rad21 subunit of cohesin ring embracing sister chromatids since S phase, opening ring, while cyclin B destruction drops CDK1 activity permitting phosphatase activation and mitotic exit. Blocking securin degradation prevents chromatid separation. This circuitry is highly conserved across eukaryotes, integrating growth factor signals, DNA damage surveillance, and developmental cues, and its disruption frequently underlies oncogenesis, providing targets for checkpoint inhibitors and cancer therapeutics.