A unified model for the origin of DNA sequence‐directed curvature

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Abstract
The fine structure of the DNA double helix and a number of its physical properties depend upon nucleotide sequence. This includes minor groove width, the propensity to undergo the B‐form to A‐form transition, sequence‐directed curvature, and cation localization. Despite the multitude of studies conducted on DNA, it is still difficult to appreciate how these fundamental properties are linked to each other at the level of nucleotide sequence. We demonstrate that several sequence‐dependent properties of DNA can be attributed, at least in part, to the sequence‐specific localization of cations in the major and minor grooves. We also show that effects of cation localization on DNA structure are easier to understand if we divide all DNA sequences into three principal groups: A‐tracts, G‐tracts, and generic DNA. The A‐tract group of sequences has a peculiar helical structure (i.e., B*‐form) with an unusually narrow minor groove and high base‐pair propeller twist. Both experimental and theoretical studies have provided evidence that the B*‐form helical structure of A‐tracts requires cations to be localized in the minor groove. G‐tracts, on the other hand, have a propensity to undergo the B‐form to A‐form transition with increasing ionic strength. This property of G‐tracts is directly connected to the observation that cations are preferentially localized in the major groove of G‐tract sequences. Generic DNA, which represents the vast majority of DNA sequences, has a more balanced occupation of the major and minor grooves by cations than A‐tracts or G‐tracts and is thereby stabilized in the canonical B‐form helix. Thus, DNA secondary structure can be viewed as atug of warbetween the major and minor grooves for cations, with A‐tracts and G‐tracts each having one groove that dominates the other for cation localization. Finally, the sequence‐directed curvature caused by A‐tracts and G‐tracts can, in both cases, be explained by the cation‐dependent mismatch of A‐tract and G‐tract helical structures with the canonical B‐form helix of generic DNA (i.e., a cation‐dependent junction model). © 2003 Wiley Periodicals, Inc. Biopolymers 69: 144–159, 2003