title: X-ray and solution studies of DNA oligomers and implications for the structural basis of A-tract-dependent curvature.
abstract: DNA containing short periodic stretches of adenine residues (known as A-tracts), which are aligned with the helical repeat, exhibit a pronounced macroscopic curvature. This property is thought to arise from the cumulative effects of a distinctive structure of the A-tract. It has also been observed by gel electrophoresis that macroscopic curvature is largely retained when inosine bases are introduced singly into A-tracts but decreases abruptly for pure I-tracts. The structural basis of this effect is unknown. Here we describe X-ray and gel electrophoretic analyses of several oligomers incorporating adenine or inosine bases or both. We find that macroscopic curvature is correlated with a distinctive base-stacking geometry characterized by propeller twisting of the base-pairs. Regions of alternating adenine and inosine bases display large propeller twisting comparable to that of pure A-tracts, whereas the values observed for pure I-tracts are significantly smaller. We also observe in the crystal structures that propeller twist leads to close cross-strand contacts between amino groups from adenine and cytosine bases, indicating an attractive NH-N interaction, which is analogous to the NH-O interaction proposed for A-tracts. This interaction also occurs between adenine bases across an A-T step and may explain in part the different behavior of A-T versus T-A steps in the context of A-tract-induced curvature. We also note that hydration patterns may contribute to propeller-twisted conformation. Based on the present data and other structural and biophysical studies, we propose that DNA macroscopic curvature is related to the structural invariance of A-tract and A-tract-like regions conferred by high propeller twist, cross-strand interactions and characteristic hydration. The implications of these findings to the mechanism of DNA bending are discussed.
authors.affiliation: Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Shatzky-Schwartz
authors.forename: N D
authors.initials: ND
authors.lastname: Arbuckle
authors.forename: M
authors.initials: M
authors.lastname: Eisenstein
authors.forename: D
authors.initials: D
authors.lastname: Rabinovich
authors.forename: A
authors.initials: A
authors.lastname: Bareket-Samish
authors.forename: T E
authors.initials: TE
authors.lastname: Haran
authors.forename: B F
authors.initials: BF
authors.lastname: Luisi
authors.forename: Z
authors.initials: Z
authors.lastname: Shakked
mesh_terms: D000225:Adenine / Q000737:chemistry; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D007288:Inosine / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D009838:Oligodeoxyribonucleotides; D014867:Water; D007288:Inosine; D004247:DNA; D000225:Adenine