Effect of the methyl group on DNA bending and curvature: structure of d(GA4U4C)2 in solution

NMR studies on d(GA4T4C)2 and d(GT4A4C)2 indicated two important factors that contribute to intrinsic DNA bending in polymers containing A/T tracts [Sarma, M.H., et al. (1988) Biochemistry 27, 3423; Gupta, G., et al. (1988) Biochemistry 27, 7909]. They are (i) propeller-twisted A.T pairs with associated bifurcated H bonds inside the A/T tract and (ii) the base sequence that joins the two neighboring A/T tracts. As an extension of our bending project, we carried out quantitative NMR studies on the decamer d(GA4U4C)2, a structural analogue of d(GA4T4C)2, to examine the effect of the methyl group on DNA bending. On the basis of quantitative NMR analysis, we arrive at the following results. (i) The decamer d(GA4U4C)2 adopts the gross morphology of a right-handed B-DNA duplex with A and U nucleotides belonging to C2'-endo,anti domain. (ii) A.U pairs are propeller twisted and hence can result in an array of interstrand bifurcated H bonds involving N6 of A and O4 of U (one base pair apart) inside the A/U tract. (iii) The orientations of A and U with respect to the long axis of the molecule are different; as a result, at the A5-U6 sequence that joins the two A/U tracts, two neighboring frames of reference do not exactly coincide in space and a junction is created at A5-U6. (iv) Inside the A/U tract, intrastrand stacking is more compact (average separation between secessive base planes being 3.2 A) than at the A5-U6 junction, where average separation between the base planes of A5 and U6 is 3.6 A.(ABSTRACT TRUNCATED AT 250 WORDS)