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Cell Cycle Commitment and the Origins of Cell Cycle Variability.

Robert F Brooks1,2

  • 1Molecular and Clinical Sciences Research Institute, St George's, University of London, London, United Kingdom.

Frontiers in Cell and Developmental Biology
|August 9, 2021
PubMed
Summary

Cellular responses to growth signals are highly variable. This review explores how the RB-E2F and APC/CCDH1 molecular networks create cell cycle heterogeneity and bistability.

Keywords:
APC/CCDH1 switchRB-E2F switchbistable switchescell cycle variabilityheterogeneityquiescencerestriction pointtransition probability

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biophysics

Background:

  • Cellular exit from quiescence is asynchronous, showing significant heterogeneity even in clonal populations.
  • Some cells enter the cell cycle with sub-optimal signals, while others require stronger stimuli, indicating variable responsiveness.
  • This variability is crucial for understanding cell cycle commitment and population dynamics.

Purpose of the Study:

  • To review the origins of variability and heterogeneity in cell cycle re-entry from quiescence.
  • To examine commitment decisions in continuously cycling cell populations.
  • To elucidate the role of the RB-E2F and APC/CCDH1 molecular networks in cell cycle dynamics.

Main Methods:

  • Review of existing literature on cell cycle regulation and heterogeneity.
  • Analysis of the properties of the RB-E2F and APC/CCDH1 molecular networks.
  • Discussion of the relationship between these networks and the Restriction Point.

Main Results:

  • The RB-E2F and APC/CCDH1 networks exhibit bistability, contributing to cell cycle heterogeneity.
  • These molecular switches likely explain kinetic behaviors described by Transition Probability models.
  • The interplay of these networks influences cell commitment decisions and response to mitogenic signals.

Conclusions:

  • Bistable molecular networks, specifically RB-E2F and APC/CCDH1, are key drivers of cell cycle heterogeneity and asynchronous re-entry from quiescence.
  • Understanding these switches provides insight into the dynamic behavior of cell populations and the Restriction Point.
  • This variability is fundamental to cellular decision-making processes in proliferation.