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Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Physiol. | doi: 10.3389/fphys.2019.01022

Quantitative Studies for Cell-division Cycle Control

  • 1RIKEN, Japan
  • 2Cellular Informatics Laboratory, RIKEN, Japan
  • 3Nara Medical University, Japan

The cell-division cycle (CDC) is driven by cyclin-dependent kinases (CDKs). Mathematical models based on molecular networks, as revealed by experimental data from molecular and genetic studies, have reproduced the oscillatory behavior of CDK activity. Thus, one basic system for representing the CDC is a biochemical oscillator (CDK oscillator). However, genetically clonal cells divide with marked variability in their total duration of a single CDC round, exhibiting non-Gaussian statistical distributions. Therefore, the CDK oscillator model does not account for the statistical nature of cell-cycle control. Herein, we review quantitative studies of the statistical properties of the CDC. Over the past 70 years, studies have shown that the CDC is driven by a cluster of molecular oscillators. The CDK oscillator is coupled to transcriptional and mitochondrial metabolic oscillators, which cause deterministic chaotic dynamics for the CDC. Recent studies in animal embryos have raised the possibility that the dynamics of molecular oscillators underlying CDC control are affected by allometric volume scaling among the cellular compartments. Considering these studies, we discuss the idea that a cluster of molecular oscillators embedded in different cellular compartments coordinates cellular physiology and geometry for successful cell divisions.

Keywords: CDK (cyclin-dependent kinase), cyclin, Transition probability, circadian oscillator, Ultradian oscillator, Metabolic oscillator, Chaos, dynamical systems

Received: 21 May 2019; Accepted: 24 Jul 2019.

Edited by:

Matteo Barberis, University of Surrey, United Kingdom

Reviewed by:

Marti Aldea, Instituto de Biología Molecular de Barcelona (IBMB), Spain
Claude Gérard, Duve Institute, Catholic University of Louvain, Belgium  

Copyright: © 2019 Arata and Takagi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Yukinobu Arata, RIKEN, Saitama, Japan, arata@riken.jp