N7 methylation alters hydrogen-bonding patterns of guanine in duplex DNA.
N7 methylation alters hydrogen-bonding patterns of guanine in duplex DNA.
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DOI：
10.1021/jacs.5b10172
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发表时间：
2015-11-11
影响因子：
15
通讯作者：
Lee S
中科院分区：
文献类型：
--
作者：
Kou Y;Koag MC;Lee S
N7 -烷基 - 2′ - 脱氧鸟苷是DNA中的主要加合物，由各种烷基化诱变剂和药物产生。然而，N7 - 烷基化对鸟嘌呤氢键模式的影响仍知之甚少。我们使用过渡态去稳定化策略制备了含N7 - 甲基 - 2′ - 脱氧鸟苷（N7mdG）的DNA，开发了一种新型的polβ - 主客体复合物体系，并确定了N7mdG或dG与dC、dT、dG和dA配对的八种晶体结构。N7mdG:dC和N7mdG:dG的结构分别与dG:dC和dG:dG非常相似，这表明N7mdG的酮式互变异构体参与了与dC和dG的碱基配对。另一方面，N7mdG:dT的结构表明，错配形成了三个氢键，并采用类似沃森 - 克里克的几何结构而非摆动几何结构，这表明N7mdG的烯醇式互变异构体参与了其与dT的碱基配对。此外，N7mdG:dA可能通过N7mdG的烯醇式互变异构体采用了一种新型的移位反式:顺式碱基对。polβ - 主客体复合物结构揭示，当与dT或dA配对时，鸟嘌呤 - N7甲基化改变了鸟嘌呤的氢键模式，并表明N7烷基化可能通过促进鸟嘌呤罕见的烯醇式互变异构体的形成来改变鸟嘌呤的碱基配对模式。
N7-Alkyl-2′-deoxyguanosines are major adducts in DNA that are generated by various alkylating mutagens and drugs. However, the effect of the N7-alkylation on the hydrogen bonding patterns of the guanine remains poorly understood. We prepared N7-methyl-2′-deoxyguanosine (N7mdG)-containing DNA using a transition-state destabilization strategy, developed a novel polβ-host-guest-complex system and determined eight crystal structures of N7mdG or dG paired with dC, dT, dG, and dA. The structures of N7mdG:dC and N7mdG:dG are very similar to those of dG:dC and dG:dG, respectively, indicating the involvement of the keto tautomeric form of N7mdG in the base pairings with dC and dG. On the other hand, the structure of N7mdG:dT shows that the mispair forms three hydrogen bonds and adopts a Watson-Crick-like geometry rather than a wobble geometry, suggesting that the enol tautomeric form of N7mdG involves in its base pairing with dT. In addition, N7mdG:dA adopts a novel shifted anti:syn base pair presumably via the enol tautomeric form of N7mdG. The polβ-host-guest-complex structures reveal that guanine-N7 methylation changes the hydrogen bonding patterns of the guanine when paired with dT or dA and suggest that N7 alkylation may alter the base pairing patterns of guanine by promoting the formation of the rare enol tautomeric form of guanine.
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DOI：
10.1016/j.mrgentox.2009.05.006
发表时间：
2009-08
影响因子：
1.9
作者：
Boysen, Gunnar;Pachkowski, Brian F.;Nakamura, Jun;Swenberg, James A.
通讯作者：
Swenberg, James A.
影响因子：
14.9
作者：
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10.1016/j.mrfmmm.2005.05.006
发表时间：
2005-10-15
影响因子：
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影响因子：
15
作者：
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影响因子：
14.9
作者：
Koag MC;Kou Y;Ouzon-Shubeita H;Lee S
通讯作者：
Lee S