Cruzeiro-Hansson L, Goodfellow J M
Department of Crystallography, Birkbeck College, London, UK.
Carcinogenesis. 1994 Aug;15(8):1525-33. doi: 10.1093/carcin/15.8.1525.
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.
已知亚硝基化合物会诱发突变和癌症。我们研究了它们的一种产物O4-甲基胸腺嘧啶对DNA序列结构和柔韧性的影响。特别地，我们关注与修复蛋白O6-烷基鸟嘌呤-DNA烷基转移酶相互作用相关的DNA方面。一般来说，含有O4-甲基胸腺嘧啶的序列具有更大的局部曲率。O4-甲基胸腺嘧啶与腺嘌呤配对的序列具有更大的柔韧性增加区域、在大沟方向上一致的弯曲以及大沟宽度的强烈振荡。另一方面，O4-甲基胸腺嘧啶与鸟嘌呤配对的序列仅具有柔韧性增加的位点、向大沟弯曲的短区域与向小沟弯曲的位点交替出现，并且大沟宽度比典型的B-DNA更大。这些特征可能导致修复蛋白纠正两种碱基对中损伤的效率存在差异。需要更多的实验数据来得出更明确的结论。
