DNA curvature does not require bifurcated hydrogen bonds or pyrimidine methyl groups

Abstract

Short tracts of the homopolymer dA · dT confer intrinsic curvature on the axis of the DNA double helix. This phenomenon is assumed to be a consequence of such tracts adopting a stable B′-DNA conformation that is distinct from B-form structure normally assumed by other DNA sequences. The more stable B′ structure of dA·dT tracts has been attributed to several possible stabilizing factors: (1) optimal base stacking interactions consequent upon the high propeller twist, (2) bifurcated hydrogen bonds between adjacent dA·dT base-pairs, (3) stacking interactions involving the dT methyl groups, and finally (4) a putative spine of ordered water molecules in the minor groove. DNA oligodeoxynucleotides have been synthesized that enable these hypotheses to be tested; of particular interest is the combination of effects due to bifurcation (2) and methylation of the pyrimidines nucleotides (3). The data indicate that neither bifurcated hydrogen bonds nor pyrimidine methyl groups nor both are essential for DNA curvature. The data further suggest that the influence of the minor groove spine of hydration on the B′-formation is small. The experiments favor the hypothesis that base stacking interactions are the dominant force in stabilizing the B′-form structure.