p53-dependent transcription can exhibit both on off and graded response after genotoxic stress

The p53 protein is a central player in cellular response to DNA damage. Induction of p53 by DNA-damaging agents involves elevation of its steady-state level and activation of its potency as a transcription factor. In the cell population, these responses can occur either homogeneously (where every single cell responds simultaneously and similarly to its neighbor) or heterogeneously (where only some cells of a population respond and the number of these increases with increasing dose of inducer). We have studied here the p53 response to DNA-damaging agents (camptothecin, mitomycin C) in individual cells. We show that the level of p53 protein is increased in every single cell of the population homogeneously, while the p53-dependent transcription can be subject to an on/off-type response. Depending on the structure of the target promoter, p53-dependent transcription can be regulated according to the binary or graded model. The on/off-type transcriptional activation pattern of p53 defines two distinct subpopulations of cells after DNA damage.