Bistable switches as integrators and actuators during cell cycle progression

Abstract

Progression through the cell cycle is driven by bistable switches—specialized molecular circuits that govern transitions from one cellular state to another. Although the mechanics of bistable switches are relatively well understood, it is less clear how cells integrate multiple sources of molecular information to engage these switches. Here, we describe how bistable switches act as hubs of information processing and examine how variability, competition, and inheritance of molecular signals determine the timing of the Rb‐E2F bistable switch that controls cell cycle entry. Bistable switches confer both robustness and plasticity to cell cycle progression, ensuring that cell cycle events are performed completely and in the correct order, while still allowing flexibility to cope with ongoing stress and changing environmental conditions.

FRET-Based Sorting of Live Cells Reveals Shifted Balance between PLK1 and CDK1 Activities During Checkpoint Recovery

“…In this sense, the cell cycle constitutes a continuous oscillation of protein levels and activities. A complex mix of feedback and feedforward systems ensures that protein levels and activities change until being reset after cell division [2,3]. In G2 phase, feedback loops between Cyclin-Cyclin Dependent Kinases (CDK) and transcription factors such as Forkhead Box Protein M1 (FoxM1) ensure a continuous increase in protein levels required for mitosis [4][5][6].…”

Dynamic bistable switches enhance robustness and accuracy of cell cycle transitions

“…These switches provide robustness and directionality to the cell cycle and ensure the genome’s integrity. Both the ‘commitment point’, where a cell becomes committed to enter the cell cycle, and the transition from G1 to S phase have been associated to underlying bistable switches [19–22]. Later, after the cell has duplicated its DNA, there is a sudden transition from G2 to mitosis, characterized by the prompt activation of cyclin-dependent kinase 1 (Cdk1).…”

Editorial

“…Part 1 provided an overview of the common principles governing the transitions between the cell cycle phases [1], the role of metabolism in quiescence-proliferation transitions [2] and the relationship between the speed of the cell cycle and cell fate [3]. In addition, Part 1 covered how cells prepare for DNA replication during G1 and how this impacts proper DNA replication in S-phase [4], how cells control entry into mitosis [5] and, once in mitosis, how they achieve proper chromosome alignment and equal segregation of chromosomes into two daughter cells [6], and how mitotic exit is controlled to ensure appropriate temporal and spatial organisation [7].…”