MATHEMATICAL-MODEL OF THE FISSION YEAST-CELL CYCLE WITH CHECKPOINT CONTROLS AT THE G1 S, G2/M AND METAPHASE/ANAPHASE TRANSITIONS/

All events of the fission yeast cell cycle can be orchestrated by fluc tuations of a single cyclin-dependent protein kinase, the Cdc13/Cdc2 h eterodimer. The G1/S transition is controlled by interactions of Cdc13 /Cdc2 and its stoichiometric inhibitor, Rum1. The G2/M transition is r egulated by a kinase-phosphatase pair, Wee1 and Cdc25, which determine the phosphorylation state of the Tyr-15 residue of Cdc2. The meta/ana phase transition is controlled by interactions between Cdc13/Cdc2 and the anaphase promoting complex, which labels Cdc13 subunits for proteo lysis. We construct a mathematical model of fission yeast growth and d ivision that encompasses all three crucial checkpoint controls. By num erical simulations we show that the model is consistent with a broad s election of cell cycle mutants, and we predict the phenotypes of sever al multiple-mutant strains that have not yet been constructed. (C) 199 8 Elsevier Science B.V. All rights reserved.