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 fluctuations of a single cyclin-dependent protein kinase, the Cdc13/Cdc2 heterodimer. The G1/S transition is controlled by interactions of Cdc13/Cdc2 and its stoichiometric inhibitor, Rum1. The G2/M transition is regulated by a kinase-phosphatase pair, Wee1 and Cdc25, which determine the phosphorylation state of the Tyr-15 residue of Cdc2. The meta/anaphase transition is controlled by interactions between Cdc13/Cdc2 and the anaphase promoting complex, which labels Cdc13 subunits for proteolysis. We construct a mathematical model of fission yeast growth and division that encompasses all three crucial checkpoint controls. By numerical simulations we show that the model is consistent with a broad selection of cell cycle mutants, and we predict the phenotypes of several multiple-mutant strains that have not yet been constructed.
Novak
B
B
Department of Agricultural Chemical Technology, Technical University of Budapest, Hungary. bnovak@chem.bme.hu
Csikasz-Nagy
A
A
Gyorffy
B
B
Chen
K
K
Tyson
J J
JJ
D000705:Anaphase / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology*; D016213:Cyclins / Q000502:physiology; D005656:Fungal Proteins / Q000502:physiology; D016193:G1 Phase / Q000502:physiology; D016195:G2 Phase / Q000502:physiology; D008432:Mathematical Computing; D008677:Metaphase / Q000502:physiology; D008938:Mitosis / Q000502:physiology; D008954:Models, Biological; D016196:S Phase / Q000502:physiology; D012568:Schizosaccharomyces / Q000166:cytology*; D029702:Schizosaccharomyces pombe Proteins
D016213:Cyclins; D005656:Fungal Proteins; D029702:Schizosaccharomyces pombe Proteins; C087768:puc1 protein, S pombe