Electrostatic Mechanisms of DNA Deformation

Abstract

The genomes of higher cells consist of double-helical DNA, a densely charged polyelectrolyte of immense length. The intrinsic physical properties of DNA, as well as the properties of its complexes with proteins and ions, are therefore of fundamental interest in understanding the functions of DNA as an informational macromolecule. Because individual DNA molecules often exceed 1 cm in length, it is clear that DNA bending, folding, and interaction with nuclear proteins are necessary for packaging genomes in small volumes and for integrating the nucleotide sequence information that guides genetic readout. This review first focuses on recent experiments exploring how the shape of the densely charged DNA polymer and asymmetries in its surrounding counterion distribution mutually influence one another. Attention is then turned to experiments seeking to discover the degree to which asymmetric phosphate neutralization can lead to DNA bending in protein-DNA complexes. It is argued that electrostatic effects play crucial roles in the intrinsic, sequence-dependent shape of DNA and in DNA shapes induced by protein binding.

A Physical Picture of Atomic Motions within the Dickerson DNA Dodecamer in Solution Derived from Joint Ensemble Refinement against NMR and Large-Angle X-ray Scattering Data

“…For N e ) 4, this structure is derived from the average ensemble structures for 50 ensembles. 1 DNH, and DHH in one alignment medium), and 3 JH3′-P restraints but differ in the representation of the nonbonded interactions. 1GIP employs a simple repulsive van der Waals term coupled with the base-base positional database potential of mean force and the multidimensional torsion-angle database potential of mean force (13), while 1DUF uses Lennard-Jones van der Waals and electrostatic potentials (12).…”

“…Solution NMR methods have also provided structural insights into DNA (5,9,10). One approach has sought to derive very precise single structures (precision of e0.2 Å) using extensive NMR data, including not only traditional NOE-derived short (<5 Å) interproton distance restraints but also residual dipolar coupling (RDC) 1 and 31 P chemical shift anisotropy (CSA) restraints (11)(12)(13)(14)(15). The most recent of these studies suggested that although a very precise structure could be generated that satisfied the experimental data reasonably well, there was evidence of conformational heterogeneity at the level of the deoxyribose sugars since the sugar RDCs could not be fully accounted for within experimental error (15).…”

Effect of Ionic Ordering in Conductivity Experiments of DNA Aqueous Solutions

“…This structure may be rather regular due to the homogeneity of DNA backbone [9,10]. The ordering of counterions around DNA macromolecule determines the elastic properties of the double helix (bending, twisting, denaturation), DNA interaction with biologically active compounds (proteins, drugs), and compaction mechanisms of macromolecule in small volumes (chromosomes, viral capsids) [11][12][13][14][15][16]. The study of dynamical ordering of DNA counterions is of paramount importance for understanding the mechanisms of DNA biological functioning.…”

Direct measurement of the dielectric polarization properties of DNA

“…DNA-ligand binding | DNA packaging | atomic force microscopy | atomistic simulations | Poisson-Boltzmann equation E lectrostatic forces have long been recognized to inherently influence the DNA structure and interactions (1,2) including DNA bending and folding (3,4), DNA packaging (5-7), and DNA-ligand recognition (8)(9)(10), owing to the high charge density of the DNA molecule. In particular, the crucial role of coulombic forces in the binding affinity of molecules to a specific DNA sequence, such as clinically important drugs into minor grooves (9) and protein complexes into major grooves (11), has been well established (12).…”