N7甲基化改变了双重DNA中关氨酸的结模式
Yi Kou1, Myong-Chul Koag1, Seongmin Lee1
1Division of Medicinal Chemistry, College of Pharmacy, The University of Texas at Austin , Austin, Texas 78712, United States.
Journal of the American Chemical Society
|October 31, 2015
概括
在DNA中N7-化可以改变其基配对. 这项研究揭示了N7-甲基-2'-脱氧氨酸 (N7mdG) 如何与丁氨酸和氨酸形成不寻常的基对,从而可能改变DNA复制效率.
科学领域:
- 分子生物学
- 结构生物学
- DNA 损伤和修复
背景情况:
- N7-基-2'-脱氧氨酸是由变异原体和药物形成的常见DNA添加物.
- N7化对关氨酸结合的影响尚不清楚.
研究的目的:
- 研究N7化对基配对的结构后果.
- 阐明 tautomeric 形式在 N7-alkyl-2'-deoxyguanosine 错配中的作用.
主要方法:
- 合成含有N7甲基-2'-脱氧氨酸 (N7mdG) 的DNA.
- 使用了polβ-主机-客户复杂系统.
- 确定了N7mdG和dG基对的八个晶体结构.
主要成果:
- N7mdG:dC和N7mdG:dG对与标准的dG对相似,这表明酸参与.
- N7mdG:dT形成了类似沃森-克里克的错误配对,表明埃诺酸参与.
- N7mdG:dA形成了一个新型转移的anti:syn基对,可能是通过乙醇复合体.
结论:
- 关氨酸-N7甲基化改变了与氨酸和氨酸的结模式.
- 化N7可能会促进古安因的罕见型,影响基因配对和潜在的DNA复制精度.
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