Sequence‐Dependent Specific p53‐Response Element Interactions Direct P53 organization and Control Transcription Selectivity

The p53‐response elements (p53‐REs) are a group of 20‐bp DNA segments spreading all over the genome that have diverse biological functions such as apoptosis or DNA repair upon binding to p53 and other proteins. Because p53‐REs are very similar to each other, differing by 1 or 2 base pairs in many cases, it is of importance to understand how cells mediate p53 and its REs interactions to enact a specific biological function. Here, we propose that among the major interactions between p53 and its REs involving Lys120, Arg280 and Arg248, the Lys120 interaction partner is variable, depending on the DNA sequence while the interactions of other residues are less so. The outcome of simulations of 6 p53‐REs complexes shows that the variance of the interaction patterns between each p53 core domain and DNA triggers the change of organization of tetrameric p53 and the different fluctuations of residues away from the interaction sites, a phenomenon of DNA‐originated allosteric effect. Further biological events depend on the presence and the level of other proteins that are able to bind the unique p53 surface caused by the specific p53‐RE binding.