Figure 1

Proposed mechanism of cell cycle regulation in budding yeast: (top) overview; (bottom) mechanistic details of the ‘modules’. Solid arrows represent reactions of synthesis, degradation, complex formation, phosphorylation and dephosphorylation, and translocations. The rectangle+oval icon represents a protein complex, and the four small ovals represent end-products of proteolysis reactions. Dashed lines with arrowhead or bar head represent, respectively, activation or inhibition of a reaction, a substance, or a module by a substance or a module. Also a protein name written along a reaction arrow indicates the catalysis of the reaction by the protein. To simplify the model, we combine cyclins with similar functions: Cln1+Cln2=‘Cln2’, Clb5+Clb6=‘Clb5’, and Clb1+Clb2=‘Clb2’. The kinase partner, Cdk1, of each cyclin is not indicated in the diagram, because we assume (justifiably) that Cdk1 is in excess and that it combines rapidly and strongly with any available cyclin molecules. Cln2, Clb5, and Clb2 are primarily responsible for initiating bud formation, DNA synthesis and mitosis, respectively, although there is some overlap of function among these cyclin-dependent kinases. The cyclin-dependent kinase inhibitor, CKI, refers to both Sic1 and Cdc6, which are stoichiometric inhibitors of Clb-dependent kinases. For a full and precise description of the model, see the set of kinetic equations in Supplementary Table S2.