X-RAY AND SOLUTION STUDIES OF DNA OLIGOMERS AND IMPLICATIONS FOR THE STRUCTURAL BASIS OF A-TRACT-DEPENDENT CURVATURE

Citation
M. Shatzkyschwartz et al., X-RAY AND SOLUTION STUDIES OF DNA OLIGOMERS AND IMPLICATIONS FOR THE STRUCTURAL BASIS OF A-TRACT-DEPENDENT CURVATURE, Journal of Molecular Biology, 267(3), 1997, pp. 595-623
Citations number
82
Categorie Soggetti
Biology
ISSN journal
00222836
Volume
267
Issue
3
Year of publication
1997
Pages
595 - 623
Database
ISI
SICI code
0022-2836(1997)267:3<595:XASSOD>2.0.ZU;2-V
Abstract
DNA containing short periodic stretches of adenine residues (known as A-tracts), which are aligned with the helical repeat, exhibit a pronou nced 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 i s largely retained when inosine bases are introduced singly into A-tra cts 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 disti nctive base-stacking geometry characterized by propeller twisting of t he base-pairs. Regions of alternating adenine and inosine bases displa y large propeller twisting comparable to that of pure A-tracts, wherea s the values observed for pure I-tracts are significantly smaller. We also observe in the crystal structures that propeller twist leads to c lose cross-strand contacts between amino groups from adenine and cytos ine bases, indicating an attractive NH-N interaction, which is analogo us to the NH-O interaction proposed for A-tracts. This interaction als o occurs between adenine bases across an A-T step and may explain in p art 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 con tribute to propeller-twisted conformation. Based on the present data a nd other structural and biophysical studies, we propose that DNA macro scopic curvature is related to the structural invariance of A-tract an d 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. (C) 1997 Acade mic Press Limited.