Practice question

Mitotic exit and establishment of G1 phase require elimination of mitotic cyclins that maintain high CDK1 activity and inhibition of microtubule dynamics regulators. While APC/C activated by Cdc20 initiates anaphase by degrading securin and partially degrading cyclin B, a second wave driven by APC/C bound to Cdh1, also known as Hct1, completes program. APC/C-Cdh1 recognizes distinct destruction box and KEN box motifs in substrates including remaining Clb2 and Clb5 cyclins in yeast, cyclin A and cyclin B1 in mammals, polo-like kinase Plk1, Aurora kinases A and B, and Cdc20 itself, targeting them for proteasomal degradation during late mitosis and early G1. Degradation results in loss of CDK1 activity, allowing activation of phosphatases and reassembly of nuclear envelope, chromosome decondensation, and licensing of replication origins. APC/C-Cdh1 also stabilizes G1 by preventing premature S-phase entry. Phosphorylation of Cdh1 by CDKs in S and early M phases inhibits it, restricting activity to period of low CDK activity. Thus role of APC/C-Cdh1 is to promote mitotic exit by degrading mitotic cyclins and associated mitotic regulators, coordinating cytoskeletal remodeling with cell cycle reset.