Critical slowing down and attractive manifold: A mechanism for dynamic robustness in the yeast cell-cycle process

Biological processes that execute complex multiple functions, such as the cell cycle, must ensure the order of sequential events and maintain dynamic robustness against various fluctuations. Here, we examine the mechanisms and fundamental structure that achieve these properties in the cell cycle of the budding yeast Saccharomyces cerevisiae. We show that this process behaves like an excitable system containing three well-decoupled saddle-node bifurcations to execute DNA replication and mitosis events. The yeast cell-cycle regulatory network can be divided into three modules-the G1/S phase, early M phase, and late M phase- wherein both positive feedback loops in each module and interactions among modules play important roles. Specifically, when the cell-cycle process operates near the critical points of the saddle-node bifurcations, a critical slowing down effect takes place. Such interregnum then allows for an attractive manifold and sufficient duration for cell-cycle events, within which to assess the completion of DNA replication and mitosis, e.g., spindle assembly. Moreover, such arrangement ensures that any fluctuation in an early module or event will not transmit to a later module or event. Thus, our results suggest a possible dynamical mechanism of the cell-cycle process to ensure event order and dynamic robustness and give insight into the evolution of eukaryotic cell-cycle processes.