Solution structure of a nonpolar, non-hydrogen-bonded base pair surrogate in DNA

We describe the structure in aqueous solution of a DNA duplex containing a base pair that is structurally analogous to A-T but which lacks hydrogen bo nds. Base analogues F (a nonpolar isostere of thymine) and Z (a nonpolar is ostere of adenine) are paired opposite one another in a 12 base pair duplex . The sequence context is the binding site of recently studied transcriptio n factor hSRY. The Z-F pair has been shown to be replicated surprisingly we ll and selectively by DNA polymerase enzymes, considering that it is destab ilizing and lacks Watson-Crick hydrogen bonds. The enzymatic studies led to the suggestion that part of the functional activity arises because the pai r resembles a natural one in geometry. The present results show that, despi te the absence of Watson-Crick hydrogen bonds, the Z-F pair structurally re sembles an A-T pair in the same context. This lends support to the proposal that shape matching is an important component in replication, and suggests the general utility of using Z-F as a nonpolar replacement for A-T in prob ing protein-DNA interactions.