title: Structure-related properties of the mutagenic lesion 6-O-methylguanine in DNA.
abstract: Chemical probing of the structures of a few very similar 30 base-pair duplexes containing a 6-O-methylguanine (meG) residue at the 16th position reveals that the modified base simultaneously perturbs the helical structure in two ways; it preferentially unstacks the 3' neighbouring base residue (thymine in this study) on the same strand and it unstacks the pyrimidine to which it is base-paired. Depending on its neighbouring 5' base residue and the base-pairing pyrimidine, this perturbation can extend to a few base-pairs in both 3' and 5' directions from the abnormal base-pair. These perturbations can be detected by cleavage at the site for the restriction enzyme MaeII. The unstaking of the C in the meG.C and A.C base-pairs may explain the de novo methylation of these helices by the human DNA-(cytosine-5-)methyltransferase. Interestingly, the kinetics of repair of the 6-O-methylguanine-containing dinucleotides by the cloned human methylguanine methyltransferase appears to be largely determined by the strength of the stacking interaction between the 6-O-methylguanine and the 5' neighbouring base.
authors: Chemical Carcinogenesis Laboratory, National University of Singapore.
authors: C W
authors: CW
authors: Wong
authors: N W
authors: NW
authors: Tan
authors: B F
authors: BF
authors: Li
mesh_terms: D001482:Base Composition; D001483:Base Sequence; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D015252:Deoxyribonucleases, Type II Site-Specific; D006147:Guanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D006860:Hydrogen Bonding; D019811:Hydroxylamine; D006898:Hydroxylamines / Q000494:pharmacology; D008780:Methyltransferases / Q000378:metabolism; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009690:Nucleic Acid Conformation; D019853:O(6)-Methylguanine-DNA Methyltransferase; D009838:Oligodeoxyribonucleotides / Q000737:chemistry* / Q000378:metabolism
chemical_list: D006898:Hydroxylamines; D009838:Oligodeoxyribonucleotides; D019811:Hydroxylamine; D006147:Guanine; C008449:O-(6)-methylguanine; D008780:Methyltransferases; D004248:DNA (Cytosine-5-)-Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase; C040837:endodeoxyribonuclease MaeII; D015252:Deoxyribonucleases, Type II Site-Specific