Figure 5. p53-mediated perturbation of DNA damage response pathways that affect mutagenesis.

A negative feedback motif composed of p53, Mdm2, and others (not shown) can produce undamped oscillations in response to radiation-induced double strand breaks. A partial AND (pAND) gate is used to indicate that to produce inheritable mutations, both DNA damage and cell proliferation (DNA replication) are required, and that the two processes likely contribute to mutagenesis in a multiplicative manner. Activation of the apoptosis pathway works to mitigate mutagenesis by killing cells with severe or unrepairable DNA damage. Pointed arrows indicate activation and blunted arrows indicate inhibition.