Molecular structure of the G.A base pair in DNA and its implications for the mechanism of transversion mutations.

The synthetic deoxydodecamer d(C-G-C-G-A-A-T-T-A-G-C-G) was analyzed by x-ray diffraction methods, and the structure was refined to a residual error of R = 0.17 at 2.5-A resolution (2 sigma data) with 83 water molecules located. The sequence crystallizes as a full turn of a B-DNA helix and contains 2 purine X purine (G.A) base pairs and 10 Watson-Crick base pairs. The analysis shows conclusively that adenine is in the syn orientation with respect to the sugar moiety whereas guanine adopts the usual trans orientation. Nitrogen atoms of both bases are involved in hydrogen bonding with the N-1 of guanine 2.84 A from the N-7 of adenine and the N-6 of adenine within 2.74 A of the O-6 of guanine. The C-1'...C-1' separation is 10.7 A close to that for standard Watson-Crick base pairs. The incorporation of the purine.purine base pairs at two steps in the dodecamer causes little perturbation of either the local or the global conformation of the double helix. Comparison of the structural features with those of the G.T wobble pair and the standard G.C pair suggests a rationale for the differential enzymatic repair of the two types of base-pair mismatches.