Chemical determinants of DNA bending at adenine-thymine tracts

Abstract

DNA fragments having homopolymeric adenine-thymine tracts phased with the helix screw are known to be bent. According to our working model, adenine-thymine tracts adopt a polymorphic structure (H-DNA), and juxtaposition of H-DNA with B-DNA results in bending at the junction between the two structures. We incorporated different base analogues in addition to the four ordinary bases into oligonucleotides; ligated multimers of oligonucleotide duplexes were run on polyacrylamide gels. By comparison of gel mobility data for different sequences, we identified factors both necessary and irrelevant for bending, corresponding to the formation of H-DNA. The 5-methyl group on pyrimidines is not essential, and the 2-amino group on purines interferes with the formation of H-DNA, either because it provides a third H bond between the bases or because it alters water structure in the minor groove. The strong base stacking of A may be an important contributing factor to stabilization of the anomalous DNA structure responsible for bending.