Adaptive Response Enzyme AlkB Preferentially Repairs 1-Methylguanine and 3-Methylthymine Adducts in Double-Stranded DNA.
Adaptive Response Enzyme AlkB Preferentially Repairs 1-Methylguanine and 3-Methylthymine Adducts in Double-Stranded DNA.
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DOI：
10.1021/acs.chemrestox.5b00522
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发表时间：
2016-04-18
影响因子：
4.1
通讯作者：
Li D
中科院分区：
文献类型：
--
作者：
Chen F;Tang Q;Bian K;Humulock ZT;Yang X;Jost M;Drennan CL;Essigmann JM;Li D
AlkB蛋白是一种利用α-酮戊二酸/Fe（II）依赖性机制修复烷基DNA加合物的修复酶。据报道，AlkB在ss-DNA中比在ds-DNA中更有效地修复高度敏感的底物，如1-甲基腺嘌呤和3-甲基胞嘧啶。在这里，我们测试了较弱的AlkB底物1-甲基鸟嘌呤和3-甲基胸腺嘧啶的修复，发现AlkB更喜欢在ds-DNA中修复它们。我们还发现AlkB及其人类同源物ABH 2和ABH 3能够修复上述加合物，当加合物存在于错配的碱基对中时。这些观察结果表明AlkB在不同环境中修复各种加合物时具有很强的适应性。
The AlkB protein is a repair enzyme that uses an α-ketoglutarate/Fe(II)-dependent mechanism to repair alkyl DNA adducts. AlkB has been reported to repair highly susceptible substrates, such as 1-methyladenine and 3-methylcytosine, more efficiently in ss-DNA than in ds-DNA. Here, we tested the repair of weaker AlkB substrates 1-methylguanine and 3-methylthymine, and found that AlkB prefers to repair them in ds-DNA. We also discovered AlkB and its human homologs, ABH2 and ABH3, are able to repair the aforementioned adducts when the adduct is present in a mismatched base pair. These observations demonstrate the strong adaptability of AlkB on repairing various adducts in different environments.