DNA-CONFORMATION IS AN IMPORTANT DETERMINANT OF SEQUENCE-SPECIFIC DNA-BINDING BY TUMOR-SUPPRESSOR P53

Sequence-specific transactivation of target genes is one of the most i mportant molecular properties of the tumor suppressor p53. Binding of p53 to its target DNAs is tightly regulated, with modifications in the carboxyterminal regulatory domain of the p53 protein playing an impor tant role. In this study we examined the possible influence of DNA str ucture on sequence-specific DNA binding by p53, by analysing its bindi ng to p53 consensus elements adopting different conformations. We foun d that p53 has the ability to bind to consensus elements which are pre sent 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 depend ent on its sequence symmetry, and is strongly influenced by its sequen ce environment. Our data suggest a model according to which the confor mational status of the target DNA is an important determinant for sequ ence-specific DNA binding by p53. Modifications in the carboxy-termina l regulatory region of p53 possibly determine the preference of p53 fo r a given DNA conformation.