X-ray analysis of DNA fragments with potential mispairs cannot give any information about the tran-
sient occurrence of rare tautomeric forms at the instant of replication. However, it can define the structure
of a DNA duplex, which incorporates mismatched base pairs and provides details of the hydrogen bond-
ing scheme, the response of the duplex to the mismatch, the influence of neighbouring sequence on the
structure and stability of the mismatch, and the effect of global conformation.^20 All these are intended to
provide clues about the ways in which mismatches might be recognised by the proteins that constitute
repair systems. High-resolution NMR studies have extended the picture to solution conformations. The
different types of base pair mismatch can be grouped into transition mismatches, which pair a purine with
the wrong pyrimidine, and transversion mismatches, which pair either two purines or two pyrimidines.
2.3.2.1 Transition Mismatches. The GT base pair has been observed in crystal structures for A-, B-
and Z-conformations of oligonucleotides. In every case it has been found to be a typical ‘wobble’pair hav-
ing anti–antiglycosylic bonds. The structure of the dodecamer, d(CGCGAATTTGCG), which has two
GT-9 mismatches, can be superimposed on that of the regular dodecamer and shows excellent corres-
pondence of backbone atomic positions.
The AC pair has been examined in the dodecamer d(CGCAAATTCGCG) and once again the two A-4C
mismatches are typical ‘wobble’ pairs, achieved by the protonation of adenine-N-1 (Figure 2.22). It is
notable that there is no significant worsening of base-stacking and little perturbation of the helix conform-
ation. However, it appears that no water molecules are bonded to these bases in the minor groove.
2.3.2.2 Transversion Mismatches. The GA mismatch is thoroughly studied in the solution and solid
states and two different patterns have been found. Crystals of the dodecamer d(CGCGAATTAGCG) have
an (anti)GA(syn) mismatch with hydrogen bonds from Ade-N-7 to Gua-N-1 and from Ade-N-6 to Gua-O-6
(Figure 2.23). A similar (anti)IA(syn) mismatch has been identified in a related dodecamer structure.
Calculations on both of these mismatches suggest that they can be accommodated into a regular B-helix
with minimal perturbation.
This work contrasts with both NMR and X-ray studies on d(CGAAGATTGG) and NMR work on
d(CGAGAATTCGCG), which have identified (anti)GA(anti) pairings with two hydrogen bonds. The
X-ray analysis of the dodecamer shows a typical B-helix with a broader minor groove and a changed
DNA and RNA Structure 37
Figure 2.22 ‘Wobble’pairs for transition mismatches GT (left) and AC (right)