Abstract
In this paper, a delayed mathematical model was developed based on experimental data to understand how the time delays required for transcription and translation in Mdm2 gene expression affect the kinetic behavior of the p53-Mdm2 network. Taking the time delays as the main research parameters, the stability of the system at the positive equilibrium was studied by using the theoretical method of delay differential equation. We found that such delays can induce oscillations by undergoing a supercritical Hopf bifurcation. Then, we used the normal form theory and the center manifold reduction to study the direction and stability of the bifurcation in detail. Furthermore, we also studied the effects of the length of time delays and the model parameters by numerical simulations. We found that time delays in Mdm2 synthesis are required for p53 oscillations and the length of such delays can determine the amplitude and period of the oscillations. In addition, the model parameters can also change the stability of the system. These results illustrate that the repair process after DNA damage can be regulated by varying time delays and the model parameters.
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