A plausible model for the digital response of p53 to DNA damage

The single-cell response of p53 to ionizing radiation (IR) is such that the number of oscillations of p53 shows dependence on the radiation dose. We present a model of this phenomenon. In our model, double strand break (DSB) sites induced by IR interact with a limiting pool of DNA repair proteins, forming complexes that are sensed by ATM, a protein kinase that activates p53 once phosphorylated by DNA damage. The ATM sensing module switches on or off the downstream p53-mdm2 negative feedback loop. Our simulations show that by assuming stochasticity in the initial number of DSBs and the DNA repair process, p53 and Mdm2 exhibit a coordinated oscillatory dynamics upon IR stimulation in single cells, with a stochastic number of oscillations whose mean increases with IR dose.