Mathematical modeling of p53 pulses in G2 phase with DNA damage

摘要

A mathematical model of p53 pulses involved in G2/M phase transition is proposed to study the response of p53-centered signaling network and checkpoint mechanisms of G2 phase to DNA damages. The oscillation by p53-Mdm2 feedback loop as the response to DNA damage is first simulated. This follows by modeling the signaling network in G2 phase and realizing its importance in cell cycle progression. The signaling network is used to assess effects of different intensities of DNA damage on G2 phase transition. An examination of the dynamics of cell fate decision module shows that p53 arrester and Wip1 play key roles in DNA repair and may be an important target of cancer therapy. The present numerical analysis based on the proposed model may be useful for the inference of p53-mediated mechanisms in response to DNA damage in G2 phase under different damage conditions.