Flexibility and curvature of DNA duplexes containing O4-methylthymine: implications for DNA repair.
Nitroso compounds are known to induce mutations and cancer. We study the effect of one of their products, O4-methylthymine, on the structure and flexibility of DNA sequences. In particular, we focus on aspects of DNA that are relevant for the interaction with the repair protein, O6-alkylguanine-DNA alkyltransferase. In general, sequences that contain O4-methylthymine have greater local curvatures. Sequences in which O4-methylthymine is paired with adenine have larger regions of increased flexibility, a consistent bend in the direction of the major groove and strong oscillations in the major groove widths. On the other hand, sequences in which O4-methylthymine is paired with guanine have only sites of increased flexibility, short regions bent towards the major groove alternating with sites bent toward the minor groove and larger major groove widths than those of canonical B-DNA. These features may possibly lead to the difference in the efficiency with which repair proteins correct the lesions in the two base pairs. Further experimental data are needed to make more definitive conclusions.
Cruzeiro-Hansson
L
L
Department of Crystallography, Birkbeck College, London, UK.
Goodfellow
J M
JM
D000478:Alkylation; D001483:Base Sequence; D004247:DNA / Q000737:chemistry*; D004260:DNA Repair; D006860:Hydrogen Bonding; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D013941:Thymine / Q000031:analogs & derivatives* / Q000737:chemistry
C021223:O-4-methylthymine; D004247:DNA; D013941:Thymine