Sequence-directed curvature of DNA

Abstract

DNAs from both prokaryotic1–4 and eukaryotic5–8 organisms have yielded restriction fragments which manifest markedly anomalous electrophoretic behaviour (reduced mobility) when run on polyacrylamide gels. We have shown previously9 that the abnormal electrophoretic behaviour of one such fragment is a consequence of stable curvature of the helix axis in solution. The molecules involved tend to contain oligo(dA)–oligo(dT) runs which are approximately in-phase with the helix repeat7,8,10; however, the precise structural elements responsible for DNA curvature have not been identified. One popular model11,12 for curvature invokes a non-coplanar ‘wedge-like’ conformation of ApA/TpT dinucleotide pairs. Despite a lack of direct evidence in support of this model, it has been used to provide quantitative estimates of curvature4,13,14. To critically evaluate the ApA wedge model, we have performed an electrophoretic analysis of a series of closely related DNA polymers in which oligo(dA)–oligo(dT) runs of different polarity were compared. We conclude that ApA dinucleotide wedges cannot account for DNA curvature. Therefore, quantitative estimates for ApA wedge deformations, based solely on apparent curvature, cannot be correct.