A feedback loop of conditionally stable circuits drives the cell cycle from checkpoint to checkpoint.

ABSTRACT: We perform logic-based network analysis on a model of the mammalian cell cycle. This model is composed of a Restriction Switch driving cell cycle commitment and a Phase Switch driving mitotic entry and exit. By generalizing the concept of stable motif, i.e., a self-sustaining positive feedback loop that maintains an associated state, we introduce the concept of a conditionally stable motif, the stability of which is contingent on external conditions. We show that the stable motifs of the Phase Switch are contingent on the state of three nodes through which it receives input from the rest of the network. Biologically, these conditions correspond to cell cycle checkpoints. Holding these nodes locked (akin to a checkpoint-free cell) transforms the Phase Switch into an autonomous oscillator th

SUBMITTER: Deritei D 

PROVIDER: S-EPMC6848090 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature