非天然胞嘧啶碱基在 DNA 聚合酶作用下通过形成 Watson-Crick 几何结构被识别为胸腺嘧啶。
Unnatural Cytosine Bases Recognized as Thymines by DNA Polymerases by the Formation of the Watson-Crick Geometry.
机构信息
School of Life Sciences, Department of Chemical Biology and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China.
Institute of Theoretical and Computational Chemistry, College of Chemistry and Molecular Engineering and Biomedical Pioneering Innovation Center, Peking University, Beijing, 100871, China.
出版信息
Angew Chem Int Ed Engl. 2019 Jan 2;58(1):130-133. doi: 10.1002/anie.201807845. Epub 2018 Dec 5.
The emergence of unnatural DNA bases provides opportunities to demystify the mechanisms by which DNA polymerases faithfully decode chemical information on the template. It was previously shown that two unnatural cytosine bases (termed "M-fC" and "I-fC"), which are chemical labeling adducts of the epigenetic base 5-formylcytosine, can induce C-to-T transition during DNA amplification. However, how DNA polymerases recognize such unnatural cytosine bases remains enigmatic. Herein, crystal structures of unnatural cytosine bases pairing to dA/dG in the KlenTaq polymerase-host-guest complex system and pairing to dATP in the KlenTaq polymerase active site were determined. Both M-fC and I-fC base pair with dA/dATP, but not with dG, in a Watson-Crick geometry. This study reveals that the formation of the Watson-Crick geometry, which may be enabled by the A-rule, is important for the recognition of unnatural cytosines.
非天然 DNA 碱基的出现为揭示 DNA 聚合酶如何忠实解码模板上的化学信息提供了机会。此前的研究表明，两种非天然胞嘧啶碱基（称为“M-fC”和“I-fC”）是表观遗传碱基 5-甲酰胞嘧啶的化学标记加合物，可在 DNA 扩增过程中诱导 C 到 T 的转换。然而，DNA 聚合酶如何识别这种非天然胞嘧啶碱基仍然是个谜。本文通过 KlenTaq 聚合酶-主体客体复合物系统中与 dA/dG 配对的非天然胞嘧啶碱基和 KlenTaq 聚合酶活性位点中与 dATP 配对的非天然胞嘧啶碱基的晶体结构，揭示了这一机制。M-fC 和 I-fC 均以 Watson-Crick 几何构型与 dA/dATP 配对，而不与 dG 配对。这项研究表明，Watson-Crick 几何构型的形成（可能由 A 规则所允许）对于非天然胞嘧啶的识别很重要。
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