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
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.