DNA Superstructures: Relevance on Physicochemical Properties and in Recognition Mechanism with Proteins

DNA curvature is now considered of great importance in determining its physicochemical properties as well as in regulating specific interactions with proteins. The idea of deviations of B DNA double helix from a straight line was firstly advanced by Trifonov, who observed a harmonic component of the base distribution in eukaryotic nucleotide sequences and associated to this component a geometrical meaning, mainly the wedge of the AA dinucleotide [1]. This hypothesis received experimental support from the observation that some DNAs migrate more slowly than normal DNA molecules, having the same molecular weight, on polyacrylamide gel electrophoresis [2]. In the last few years, numerous research groups have spent strong efforts to correlate DNA superstructural features to the nucleotide sequence as well as to develop methods to experimentally characterize curved, with respect to straight, DNAs [3]. DNA superstructural features have resulted of great relevance in the control of important biological processes such as transcription [4] and chromatin organization [5]. Taking advantage of the theoretical method developed by De Santis and coworkers [6,7], which derives DNA curvature from the nucleotide sequence, and of the rapidly increasing number of known sequences of DNA regulative regions derived via genetic engineering, it is now possible to predict the superstructural features of these sequences and to try a correlation with their biological role. Furthermore, on the basis of theoretical curvature profiles of the investigated DNA tracts, it is easier to plan experimental approaches to verify the theoretical prediction as well as to evaluate the physicochemical properties of the considered DNAs. We want to report in the present paper two examples of biologically significant sequences studied according to this approach. The first one refers to the sequences which regulate transcription in the pea multigenic rbcS family, which code for the small subunit of ribulose bisphosphate carboxylase, a key enzyme in photosynthesis. A very satisfactory correlation between the theoretically predicted superstructural features of these sequences and their physicochemical properties, such as electrophoretic mobility, circular dichroism and cyclization probability, was found. The second system is a DNA fragment about 500 bp long, containing a highly curved sequence derived from the protozoa Crithidia fasciculata [8].