Curvature and Deformation of Nucleic Acids: Overview

Abstract

The structure of DNA proposed by Watson and Crick (1) from fiber diffraction data (2) was symmetric and highly regular, leading to the idea that DNA structure was monolithic and independent of sequence. Subsequent studies, however, especially by Arnott and coworkers (3), showed that DNA structure is in fact highly variable, and depends on hydration, base-pair composition and the identity of the counterion.Many of the early investigations of DNA conformation in solution revolved around the questions of polymer physics-the size, shape, and flexibility of the macromolecule and its stability under a variety of experimental conditions (reviews: 4-7). The modern era of DNA structural studies began when the x-ray crystal structure of a dodecamer containing the EcoRI recognition site was solved by . This structure showed that each base-pair step makes its own individual contribution to the conformation of the helix, indicating that DNA structure must be sequencedependent. A host of other x-ray and NMR studies of small DNA oligomers and DNA-drug and DNA-protein complexes followed, providing atomic-level detail about DNA structure and conformation in a variety of contexts (reviews: 6, 7, 11-14). These and other studies were made possible by concomitant advances in molecular biology and the development of methods for automated oligonucleotide synthesis, which made it possible to prepare the large quantities of highly purified DNA oligomers needed for biophysical studies.

Role of Mg2+ and Ca2+ in DNA Bending: Evidence from an ONIOM-Based QM-MM Study of a DNA Fragment

“…DNA−metal ion interactions play key roles in the control of DNA conformation and its topology. − These interactions are governed by several parameters such as the nature of the metal, its size, and its charge. − All these parameters influence the conformation of DNA by direct or indirect interaction through the water molecules with the basic sites of the nucleotides − For instance, coordination of phosphate moieties by alkaline-earth cations such as Mg 2+ and Ca 2+ is essential in folding and winding of the polynucleic acids as they assume compact arrangements in vivo for catalytic enzymatic reactions involving de-esterification of phosphate esters, , stabilization of triple and quadruple helices, for the processes involving the transfer of genetic information and the synthesis of oligonucleotides…”

“…DNA-metal ion interactions play key roles in the control of DNA conformation and its topology. [1][2][3][4][5][6][7] These interactions are governed by several parameters such as the nature of the metal, its size, and its charge. [8][9][10][11][12] All these parameters influence the conformation of DNA by direct or indirect interaction through the water molecules with the basic sites of the nucleotides.…”

DNA A-tracts bending: Polarization effects on electrostatic interactions across their minor groove

“…Although a very large number of studies have been carried out and a number of models have been proposed [for reviews, see Beveridge et al, 2004;Crothers and Shakked, 1999;MacDonald and Lu, 2004;Stellwagen and Mohanty, 2004], the physical origin of the bending of DNA remains unclear. The controversial nature of the findings suggests that there are deficiencies in our understanding of the underlying physics, e.g.…”