Sequence effects on local DNA topology

Nuclear Overhauser effect-derived distances between adenine H2 protons and anomeric H1′ protons on the same strand or on the complementary strand are presented for several different DNA duplexes. The cross-strand (n)AH2 to (m + 1)H1′ distances [designated as x, where (n) and (m) are complementary residues] vary by up to 1 Å depending on the sequence. In all possible A-containing pyrimidine-purine steps (CA, TG, and TA), x is >4.5 Å. In GA steps, x varies within rather wide limits in the range 3.8-4.5 Å, whereas in AA steps the lower limit is 3.7 Å and the upper limit is ≈4.2 Å. In purine-purine steps, x is affected by at least three factors: (i) adjacent pyrimidine-purine steps at the 5′ end [e.g., YRA sequences (where Y = T or C and R = G or A)], or a pyrimidine-purine step at the 3′ end of the pyrimidine-pyrimidine step on the complementary strand, cause x to increase, (ii) an AT step at the 3′ end of a purine-purine step (e.g., RAT) causes x to decrease, and (iii) substitution of bases at the next-nearest neighbor position leads to changes in x at GA and AA steps. The latter factor seems to be due to a cooperative effect arising from formation of the "anomalous" B′ structure when the substitution produces an A_nT_m tract (which always produces a decrease in x). The data indicate that (n)AH2-(n + 1)H1′ distances on the same strand (designated as s) are also sequence dependent. Thus on AA steps, neighboring substitutions produce the same effect on s as on the cross-strand x distances. The results lead to the ability to predict changes in AH2-H1′ distances depending on the DNA sequence. By using high-resolution x-ray B-type structures as a set of allowable B conformations, a very good correlation was found between x and the minor groove width parameters P-P or H1′-H1′. Thus, the x distances are a direct probe of the minor groove width in B-type DNA, and changes in this distance therefore reflect changes in the minor groove width. Since many of the sequences studied are sites of protein recognition, the observed sequence-structure dependence in DNA probably plays an important role in the process of recognition by proteins and minor groove ligands such as drugs.