Structural Studies of DNA

Diabetes, Digestive, Kidney Diseases

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Abstract

Kornyshev and Leikin have derived a detailed theory of interactions between DNA molecules in concentrated solution. They consider the intermolecular electrostatic effects of helical surface charge patterns, including both the negative charges on the phosphate backbone of DNA and distributions of cationic ligands in the major or minor grooves or on the strands of the helix. The predicted helical charge patterns are predicted to effect molecular interactions and mutual orientations, helical symmetry, and helical parameters. These effects have direct application to major unsolved biological problems involving DNA, including the specificity of cationic ligands in DNA condensation, the sequence-specific alignment of DNA duplexes required for homologous DNA recombination, the differences in helical parameters of B DNA in dilute vs. concentrated solutions, and the adoption of cholesteric and A-form structures. Our earlier studies by X-ray fiber diffraction of B DNA conformation under conditions of controlled hydration provide a large repository of data that have been reanalyzed to test the current theory. Specifically, the theory of Kornyshev and Leikin predicts that as the separation between DNA duplexes in solution decreases, those duplexes should become mutually oriented; the resulting azimuthal correlations between molecules should then lead to a sampling on non-zero layer lines of the diffraction patterns that reflects the degree of molecular separation. The observed changes in diffraction patterns are in good agreement with this prediction, providing support to this powerful theoretical model.