Chen Fangyi, Tang Qi, Bian Ke, Humulock Zachary T, Yang Xuedong, Jost Marco, Drennan Catherine L, Essigmann John M, Li Deyu
Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island , Kingston, Rhode Island 02881, United States.
School of Pharmaceutical Science and Technology, Tianjin University , Tianjin 300072, P. R. China.
Chem Res Toxicol. 2016 Apr 18;29(4):687-93. doi: 10.1021/acs.chemrestox.5b00522. Epub 2016 Mar 15.
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 that AlkB and its human homologues, 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 toward repairing various adducts in different environments.
AlkB蛋白是一种修复酶，它利用α-酮戊二酸/铁（II）依赖性机制来修复烷基化DNA加合物。据报道，AlkB在单链DNA中比在双链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情况，发现AlkB更喜欢在双链DNA中修复它们。我们还发现，当加合物存在于错配碱基对中时，AlkB及其人类同源物ABH2和ABH3能够修复上述加合物。这些观察结果证明了AlkB在不同环境中修复各种加合物的强大适应性。
