Sequence-dependent structural effects in left-handed DNA

Abstract

About 25 years ago the DNA sequence d(CGCGCG)2 was crystallized, and the structure solved as a left-handed helix, dubbed Z-DNA. Many crystal structures of variants of this first sequence have since been obtained. In our laboratory we have focused on what happens to the helical structure, inter-helical interactions, and the solvent interactions when a single A:T (adenine–thymine) base pair replaces a G:C (guanine–cytosine) base pair in the hexameric sequence. We present here a review of these studies. The review addresses three topics. In the first part, it discusses the effect of A:T base pairs on the structure of Z-DNA. The crystal structures demonstrate that the degree of structural perturbation that an A:T base pair produces depends on its position in the sequence, as this alters the length of the G:C tract. The presence of four continuous G:C base pairs appears to be necessary and sufficient to nucleate a Z-type structure. In the second part, the review deals with interactions between helices and crystal packing modes in Z-DNA. It examines the consequences to these aspects, of the presence of an A:T base pair in the sequence. Hexameric duplexes may be approximated as cylinders. This leads to degeneracy in crystal packing modes in Z-DNA, particularly at low resolution. The presence of a single A:T base pair breaks the two-fold symmetry in the sequence and gives rise to directionality in the cylinders. This has interesting effects on the inter-helical interactions, and therefore on the crystal packing. Metal ion and solvent interactions are discussed in the third section of the review. Different ions have different modes of binding to the helices. Some of these are specific to the sequence and lead not only to subtle, but well-marked, variations in the helical structure, but also to differences in helical contacts and therefore crystal packing. In some cases they induce disorder in crystal packing. In others, the ions interact with the helices in a non-specific manner. Contents 1. Introduction 338 2. Sequence-dependent structure 339 3. Crystal packing 344 4. Solvent and ion interaction 350 Acknowledgements 353 References 353 Subject index 355