The baseline level of DNA damage is never “zero”. Endogenous sources of DNA damage provide a baseline for p53 “activation”. “Activation” is defined as transcriptional induction of p53-regulated effector genes. As DNA damage levels increase, p53 becomes phosphorylated which may promote apoptosis. A number of DNA repair proteins are involved in the p53-mediated protective mechanism, including APE/Ref-1, XPC, gadd45, and Brca1.