Figure 3

Studying the biological program governing the cell cycle in budding yeast. (a) The order of the cell cycle phases upon perturbation of G0 due to activating cell size, before the system stabilizes in G0 (indicated by a star). An example of S phase is visualized graphically on the network diagram. (b) The ABN constructed from the Yeast model proposed by Li et al. (c) The cABN satisfying the cyclic constraint in (a). 11 required interactions are indicated by solid arrows (in addition to the definite activation of Cln3 by cell size). (d) Example trajectory taken by one solution when the G0 state is perturbed by activating cell size. The step at which each cell cycle phase is reached is indicated. (e) There are 12 minimal networks, each consisting of 20 instantiated possible interactions. Green indicates an activation, red indicates a repression, and asterisks indicate required interactions. Some of these mechanisms do not require all components to behave as regulators (Mcm1, Cdh1 and Swi5). In addition, some sets of interactions expose redundancy: for example, six concrete models do not require Swi5 to regulate Sic1, which is instead activated by Cdc20. In the remaining models, Swi5 is required to activate Sic1 in the absence of activation by Cdc20. (Similarly, the activation of Cdc20 by Clb12 or Mcm1, and the inhibition of Clb12 by Cdc20, Cdh1 or Sic1.) (f) The set of consistent mechanisms can be used to predict perturbations that arrest the cell cycle. In each case, loss of function of the gene highlighted on the arrow will prevent the transition from occurring.