Abstract
Some biological networks exhibit oscillations in their components to convert stimuli to time-dependent responses. The eukaryoticcell cycle is such a case, being governed by waves of cyclin-dependent kinase (cyclin/Cdk) activities that rise and fall with specifictiming and guarantee its timely occurrence. Disruption of cyclin/Cdk oscillations could result in dysfunction through reduced celldivision. Therefore, it is of interest to capture properties of network designs that exhibit robust oscillations. Here we show that aminimal yeast cell cycle network is able to oscillate autonomously, and that cyclin/Cdk-mediated positive feedback loops (PFLs) andClb3-centered regulations sustain cyclin/Cdk oscillations, in known and hypothetical network designs. We propose that Clb3-mediated coordination of cyclin/Cdk waves reconciles checkpoint and oscillatory cell cycle models. Considering the evolutionaryconservation of the cyclin/Cdk network across eukaryotes, we hypothesize that functional (“healthy”) phenotypes require thecapacity to oscillate autonomously whereas dysfunctional (potentially“diseased”) phenotypes may lack this capacity.