Structure and Energetics of O 6-Methylguanine Pairings in Minihelical Environment: Implication to the Theory of Induced Mutations and Oncogene Activation

This chapter considers the possible mispairings of O⁶-methylguanine (mG) with thymine and cytosine. Several attempts to explain the specific promutagenic property of mG have been undertaken within the quantum-mechanical methods. Most of these works have been restricted to calculate the interaction energies of isolated base mG with thymine and cytosine without looking at backbone environment, and sequence dependence. Among the possible hydrogen bonding schemes for m⁶dG.C pairs, it seems clear that the involvement of minor tautomers is very unlikely, due to its large tautomerization energy. Surprisingly, and contrary to comprehensive biological data, very little conclusive physical evidence exists in the literature on the characterization of m⁶dG mispairs. In spite of the great significance of the conformation of the O⁶-methyl group to the nature of m⁶dG mispairs, only very recently has the structure of m⁶dG itself been determined in crystals. The significant difference in interaction energies for the pairs as obtained by C. Nagata et al. deserves some comment.