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Related Experiment Videos

A simple time delay model for eukaryotic cell cycle.

J Srividhya1, M S Gopinathan

  • 1Indiana University School of Informatics, Indiana University, Bloomington, IN 47406, USA. srividhya@iitm.ac.in

Journal of Theoretical Biology
|February 14, 2006
PubMed
Summary

We developed a cell cycle model incorporating a time delay in anaphase promoting complex (APC) activation, which functions as a spindle checkpoint. This delay influences G1 phase timing and improves reproduction of mutant phenotypes, especially with stochasticity.

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Area of Science:

  • Cell Biology
  • Mathematical Modeling
  • Systems Biology

Background:

  • The eukaryotic cell cycle is a fundamental biological process regulated by complex molecular interactions.
  • Phosphorylation-dephosphorylation (P-D) cycles, including those involving MPF, Cdc25, Wee1, and APC, are critical regulators.
  • Cell cycle checkpoints, such as the G2/M checkpoint, ensure proper progression and prevent errors.

Purpose of the Study:

  • To propose a novel mathematical model of the cell cycle in higher eukaryotes.
  • To investigate the role of time delays, specifically in APC activation, as a spindle checkpoint.
  • To explore the impact of stochasticity on cell cycle dynamics and reproduce experimental observations.

Main Methods:

  • Development of a seven-variable mathematical model incorporating four key P-D cycles.

Related Experiment Videos

  • Representation of the G2/M checkpoint using saddle-node loop bifurcation.
  • Introduction of a time lag in the activation of APC by MPF to simulate a spindle checkpoint.
  • Incorporation of stochasticity to model cell cycle time dependence on cell birth length.

    • Main Results:

    • The model demonstrates that a time delay in APC activation acts as a spindle checkpoint.
    • Absence of time delay leads to bistability, while its presence introduces variability in G1 phase.
    • The model successfully reproduces experimental data for wee1 mutant cells.
    • Stochastic simulations provide a better fit to experimental observations of mutant phenotypes compared to the deterministic model.

    Conclusions:

    • Time-delayed modeling of APC activation is crucial for accurately representing cell cycle regulation and checkpoint functions.
    • Stochasticity plays a significant role in cell cycle timing and the manifestation of mutant phenotypes.
    • The proposed model offers a robust framework for understanding cell cycle dynamics and exploring genetic perturbations.