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Mechanism of cell cycle disruption by multiple p53 pulses

Kazunari Iwamoto1, Hiroyuki Hamada, Masahiro Okamoto

  • 1Laboratory for Bioinformatics, Graduate School of Systems Life Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan. kazunari-i@brs.kyushu-u.ac.jp

Genome Informatics. International Conference on Genome Informatics
|January 11, 2012
PubMed

Insights

The tumor suppressor gene p53

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Systems Biology

Background:

  • The tumor suppressor gene p53 plays a critical role in cellular response to DNA damage, regulating cell fate.
  • Recent observations revealed p53 oscillation in MCF7 cells, but its biological significance remained unclear.

Purpose of the Study:

  • To investigate the relationship between p53 oscillation and cell cycle progression using a novel mathematical model.
  • To elucidate the biological meaning of p53 oscillation in the context of DNA damage and cell cycle regulation.

Main Methods:

  • Construction of a mathematical model integrating the cell cycle regulatory system and p53 signaling network.
  • Simulations were performed under conditions with and without DNA damage to analyze p53 dynamics and cell cycle progression.

Main Results:

  • Simulations without DNA damage aligned with existing biological findings.
  • Simulations with DNA damage demonstrated p53 oscillation and cell cycle arrest, indicating that multiple p53 pulses disrupt cell cycle progression.
  • Cell cycle disruption was attributed to M phase catastrophe, caused by decreased cyclin A/cyclin-dependent kinase 2 levels.

Conclusions:

  • The generation of multiple p53 pulses in response to DNA damage is linked to cell cycle disruption.
  • p53 oscillation may serve as a potential biomarker for cell cycle disruption following DNA damage.

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