DNA-conformation is an important determinant of sequence-specific DNA binding by tumor suppressor p53

Abstract

Sequence-specific transactivation of target genes is one of the most important molecular properties of the tumor suppressor p53. Binding of p53 to its target DNAs is tightly regulated, with modifications in the carboxy-terminal regulatory domain of the p53 protein playing an important role. In this study we examined the possible influence of DNA structure on sequence-specific DNA binding by p53, by analysing its binding to p53 consensus elements adopting different conformations. We found that p53 has the ability to bind to consensus elements which are present in a double-helical form, as well as to consensus elements which are located within alternative non-B-DNA structures. The ability of a consensus element to adopt either one of these conformations is dependent on its sequence symmetry, and is strongly influenced by its sequence environment. Our data suggest a model according to which the conformational status of the target DNA is an important determinant for sequence-specific DNA binding by p53. Modifications in the carboxy-terminal regulatory region of p53 possibly determine the preference of p53 for a given DNA conformation.