Wong C W, Tan N W, Li B F
Chemical Carcinogenesis Laboratory, National University of Singapore.
J Mol Biol. 1992 Dec 20;228(4):1137-46. doi: 10.1016/0022-2836(92)90321-a.
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.
对几个非常相似的30个碱基对的双链体结构进行化学探测，这些双链体在第16位含有一个6-O-甲基鸟嘌呤（meG）残基，结果表明，修饰后的碱基同时以两种方式扰乱螺旋结构；它优先使同一条链上3'相邻的碱基残基（本研究中为胸腺嘧啶）解堆叠，并且使与之碱基配对的嘧啶解堆叠。根据其相邻的5'碱基残基和碱基配对的嘧啶，这种扰动可以从异常碱基对向3'和5'方向延伸几个碱基对。这些扰动可以通过在限制性内切酶MaeII的位点进行切割来检测。meG.C和A.C碱基对中C的解堆叠可能解释了这些螺旋被人DNA-（胞嘧啶-5-）甲基转移酶从头甲基化的现象。有趣的是，克隆的人甲基鸟嘌呤甲基转移酶对含6-O-甲基鸟嘌呤的二核苷酸的修复动力学似乎很大程度上取决于6-O-甲基鸟嘌呤与5'相邻碱基之间堆叠相互作用的强度。
