Frequency Domain Analysis Reveals External Periodic Fluctuations Can Generate Sustained p53 Oscillation
2011

How DNA Damage Affects p53 Oscillation

publication Evidence: moderate

Author Information

Author(s): Shin Yong-Jun, Hencey Brandon, Lipkin Steven M., Shen Xiling

Primary Institution: Cornell University

Hypothesis

How does the p53-MDM2 feedback loop alter to maintain sustained p53 oscillation after DNA damage?

Conclusion

The p53-MDM2 feedback loop adapts to DNA damage by allowing periodic DNA repair-related fluctuations to modulate p53 oscillation.

Supporting Evidence

  • The p53 levels oscillate in a sustained way after DNA damage.
  • The feedback loop adapts to allow DNA repair-related signals to influence p53 oscillation.
  • Overexpression of MDM2 can disrupt the adaptive mechanism of the feedback loop.

Takeaway

When DNA is damaged, a protein called p53 starts to wiggle back and forth in a special way to help fix the damage, and this wiggling can be influenced by other signals in the cell.

Methodology

Frequency domain analysis was used to study the dynamics of the p53-MDM2 feedback loop under different cellular conditions.

Limitations

The frequency domain analysis can only be performed on a linear model, which may not capture all non-linear behaviors.

Digital Object Identifier (DOI)

10.1371/journal.pone.0022852

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