Mismatches in DNA double strands: thermodynamic parameters and their correlation to repair efficiencies

The helix-coil transitions of the 16 octadecameric DNA duplexes dCGTCGTTTXACAACGTCG X dCGACGTTGTX1AAACGACG with A, T, G, and C for X and X1 were measured by UV-absorption. This sequence was taken from former studies of in vivo determination of efficiencies of mismatch repair (Kramer, Kramer, and Fritz (1984) Cell 38, 879-887). The thermodynamic parameters for double strand and mismatch formation have been obtained by evaluating the partition function of a stack model which allowed for loop formation. As a result the mismatches could be classified into wobble base pairs (T/G, G/G, C/A, A/A, A/G), open base pairs, i.e. permanent loops (T/T, C/T, T/C, C/C), and intermediate or weak base pairs (G/T, A/C, G/A). There is no correlation between Tm and the biological repair efficiency of X/X1. The structure classes, however, as described above show a close correlation: Open base pairs show the lowest repair efficiencies, whereas mismatches with high repair efficiency always belong to the structural class of wobble base pairs. Because of the palindromic nearest neighbors of the variation site X/X1, the influence of next-nearest neighbor interactions could be detected and be estimated to about 1 kJ/mol for one stack.