FLEXIBILITY AND CURVATURE OF DNA DUPLEXES CONTAINING O-4-METHYLTHYMINE - IMPLICATIONS FOR DNA-REPAIR

Nitroso compounds are known to induce mutations and cancer. We study t he effect of one of their products, O-4-methylthymine, on the structur e and flexibility of DNA sequences. In particular, we focus on aspects of DNA that are relevant for the interaction with the repair protein, O-6-alkylguanine-DNA alkyltransferase. In general, sequences that con tain O-4-methylthymine have greater local curvatures. Sequences in whi ch O-4-methylthymine is paired with adenine have larger regions of inc reased flexibility, a consistent bend in the direction of the major gr oove and strong oscillations in the major groove widths. On the other hand, sequences in which O-4-methylthymine is paired with guanine have only sites of increased flexibility, short regions bent towards the m ajor groove alternating with sites bent toward the minor groove and la rger major groove widths than those of canonical B-DNA. These features may possibly lead to the difference in the efficiency with which repa ir proteins correct the lesions in the two base pairs. Further experim ental data are needed to make more definitive conclusions.