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.
Jõers
Arvi
A
Department of Cell Biology, Institute of Molecular and Cell Biology, Tartu University, Riia 23, 51010, Tartu, Estonia. ajoers@ebc.es
Jaks
Viljar
V
Kase
Johanna
J
Maimets
Toivo
T
D001483:Base Sequence; D015153:Blotting, Western; D004249:DNA Damage; D017931:DNA Primers; D005455:Fluorescent Antibody Technique; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000235:genetics; D009153:Mutagens / Q000633:toxicity*; D014158:Transcription, Genetic / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D017931:DNA Primers; D008164:Luminescent Proteins; D009153:Mutagens; D016159:Tumor Suppressor Protein p53; D049452:Green Fluorescent Proteins