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DNA Damage can Stall the Cell Cycle02:36

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In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
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Bifurcation in Cell Cycle Dynamics Regulated by p53.

Md Jahoor Alam1, Sanjay Kumar2, Vikram Singh3

  • 1School of Computational and Integrative Sciences, Jawaharlal Nehru University, New Delhi-110067, India; College of Applied Medical Sciences, University of Hail, Hail-2440, Kingdom of Saudi Arabia.

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Irradiation impacts p53 dynamics, causing oscillations or stabilization. The cell cycle

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Area of Science:

  • * Molecular and Systems Biology
  • * Biophysics
  • * Mathematical Biology

Background:

  • * The p53 protein is a critical regulator of cellular responses to stress, including DNA damage.
  • * Cell cycle dynamics are complex and involve intricate feedback loops between molecular species.
  • * Understanding the interplay between p53 and cell cycle networks is crucial for comprehending cellular fate decisions.

Purpose of the Study:

  • * To investigate the regulatory mechanism of p53 on cell cycle dynamics under irradiation stress.
  • * To model the interactions between p53 and cell cycle networks.
  • * To analyze the impact of irradiation strength on p53 and cell cycle molecular species.

Main Methods:

  • * Development of a mathematical model simulating interacting p53 and cell cycle networks.
  • * Analysis of p53 dynamics under varying irradiation strengths.
  • * Examination of cell cycle molecular species (MPF and cyclin) dynamics through bifurcation analysis.

Main Results:

  • * Irradiation induces distinct phases in p53 dynamics: oscillating and oscillation death (stabilized).
  • * The collapse time of p53 oscillations (Δt) is dependent on irradiation strength.
  • * Cell cycle molecular species exhibit diverse states (oscillation death, sustained oscillations, chaos) influenced by p53-mediated irradiation stress.

Conclusions:

  • * A critical threshold (Δtc) for irradiation-induced p53 dynamics exists.
  • * Below this threshold, the cell cycle may return to normal; above it, cell cycle arrest (apoptosis) is predicted.
  • * The study provides insights into p53's role in determining cell fate following DNA damage.