Practice question

After separase cleavage of cohesin and chromosome segregation, cells must eliminate remaining mitotic cyclins to establish low CDK environment permissive for origin licensing, transcription reactivation and cytokinesis in G1. Two sequential APC/C coactivators accomplish temporal ordering. APC/C-Cdc20 initiates anaphase by destroying securin and majority of cyclin B during metaphase to anaphase transition. Cdc20 itself then becomes substrate for APC/C-Cdh1. Cdh1, also known as Fzr1, associates with APC/C core from late anaphase through G1, recognizing extended degron repertoire including KEN-box, D-box and ABBA motifs. Targets include residual cyclin B, cyclin A, Plk1, Aurora kinases A and B, Cdc20, geminin, Skp2 and Ets transcription factors. Continued degradation prevents re-accumulation of CDK1-Cyclin B activity, maintaining stable G1 state that allows formation of pre-replicative complexes containing ORC, Cdc6, Cdt1 and MCM helicases. At G1/S border, Cdh1 phosphorylated by CDK2-Cyclin E and inhibited by Emi1 pseudosubstrate, allowing cyclin buildup for next S phase. Loss of Cdh1 causes persistent mitotic kinases, premature S entry and genomic instability. 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.