The structural basis of DNA curvature remains elusive, because models
for curvature based on crystallographic structures of molecules contai
ning A tracts do not agree with any of the models for sequence-directe
d curvature based on solution studies, Here we demonstrate that the di
fference is probably due to MPD (2-methyl-2,4-pentanediol), the dehydr
ating agent commonly used in crystallography, One characteristic signa
ture of curved DNA molecules is that they run anomalously slowly on po
lyacrylamide gels, appearing to be larger than they actually are, The
gel anomalies of three curved DNAs from trypanosome kinetoplast minici
rcles drop monotonically with increasing MPD concentration, indicating
that MPD straightens molecules that are curved in aqueous solution, T
his is not due to some non-specific effect of MPD on poly(dA) or polyp
urine tracts, because control molecules containing dA(70) and dG(43) r
un normally over the full range of MPD concentrations, Circular dichro
ism spectra are not affected by MPD, ruling out a conformational chang
e to a structure outside the B-DNA family, The effect is not due to MP
D-induced changes in phasing of the curved sequences, because MPD has
virtually no effect on the linking numbers of relaxed plasmids contain
ing either curved sequences or dA(70). At the concentrations of MPD us
ed in X-ray crystallography, the curvature of DNAs containing A tracts
is substantially lower than in solution, which probably explains the
ongoing discrepancies between the crystallographic results and models
based on solution studies.