A yeast cell cycle model integrating stress, signaling, and physiology

The cell division cycle in eukaryotic cells is a series of highly coordinated molecular interactions that ensure that cell growth, duplication of genetic material, and actual cell division are precisely orchestrated to give rise to two viable progeny cells. Moreover, the cell cycle machinery is responsible for incorporating information about external cues or internal processes that the cell must keep track of to ensure a coordinated, timely progression of all related processes. This is most pronounced in multicellular organisms, but also a cardinal feature in model organisms such as baker's yeast. The complex and integrative behavior is difficult to grasp and requires mathematical modeling to fully understand the quantitative interplay of the single components within the entire system. Here, we present a self-oscillating mathematical model of the yeast cell cycle that comprises all major cyclins and their main regulators. Furthermore, it accounts for the regulation of the cell cycle machinery by a series of external stimuli such as mating pheromones and changes in osmotic pressure or nutrient quality. We demonstrate how the external perturbations modify the dynamics of cell cycle components and how the cell cycle resumes after adaptation to or relief from stress.