Practice question

G2 to M transition represents bistable switch controlled by accumulation of active CDK1-Cyclin B, often termed mitosis-promoting factor. Throughout G2, Cyclin B synthesis steadily rises transcribed by FoxM1 and stabilized, yet associated CDK1 remains inactive due to inhibitory phosphorylations at Thr14 and Tyr15 catalyzed by nuclear Wee1 and cytoplasmic Myt1 kinases occupying ATP-binding pocket. At threshold, dual specificity phosphatase Cdc25B initially and subsequently Cdc25C removes these phosphates. Activating Thr161 phosphorylation by CAK complex CDK7-Cyclin H further boosts activity. Once small amount of CDK1-Cyclin B activates, it initiates powerful feedback circuits: phosphorylation and activation of Cdc25 isoforms generating positive feedback, and phosphorylation and inhibition of Wee1 plus degradation via SCF-betaTrCP producing double negative loop. Rapid autoamplification creates abrupt switch. Active CDK1-Cyclin B translocates into nucleus via importin beta and cyclin B nuclear localization signal phosphorylation, phosphorylating lamins, condensins, Golgi and microtubule motors orchestrating prophase. DNA damage checkpoint via ATR-Chk1 inhibits Cdc25 and stabilizes Wee1 to maintain G2 arrest. 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.