Mechanisms of signalling-memory governing progression through the eukaryotic cell cycle

• Published in: Current opinion in cell biology Vol. 69; pp. 7 - 16
• Main Authors: Novák, Béla, Tyson, John J.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.2021
• Subjects: Bistability; Cell cycle transition; Checkpoint; Feedback loop; G1/S transition; G2/M transition; Hysteresis; Irreversible switch; Meta/anaphase transition; Network motif; Restriction point; G1/S transition; Feedback loop; Restriction point; Checkpoint; Cell cycle transition; G2/M transition; Irreversible switch; Meta/anaphase transition; Hysteresis; Bistability; Network motif
• ISSN: 0955-0674; 1879-0410; 1879-0410
• DOI: 10.1016/j.ceb.2020.12.003

As cells pass through each replication–division cycle, they must be able to postpone further progression if they detect any threats to genome integrity, such as DNA damage or misaligned chromosomes. Once a ‘decision’ is made to proceed, the cell unequivocally enters into a qualitatively different biochemical state, which makes the transitions from one cell cycle phase to the next switch-like and irreversible. Each transition is governed by a unique signalling network; nonetheless, they share a common characteristic of bistable behaviour, a hallmark of molecular memory devices. Comparing the cell cycle signalling mechanisms acting at the restriction point, G1/S, G2/M and meta-to-anaphase transitions, we deduce a generic network motif of coupled positive and negative feedback loops underlying each transition.