Repair of 3-methylthymine and 1-methylguanine lesions by bacterial and human AlkB proteins
Repair of 3-methylthymine and 1-methylguanine lesions by bacterial and human AlkB proteins
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DOI：
10.1093/nar/gkh964
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发表时间：
2004-01-01
影响因子：
14.9
通讯作者：
Falnes, PO
中科院分区：
文献类型：
--
作者：
Falnes, PO
大肠杆菌 AlkB 蛋白通过氧化去甲基化修复 DNA 和 RNA 中的 1-甲基腺嘌呤 (1-meA) 和 3-甲基胞嘧啶 (3-meC) 损伤，该反应分别需要亚铁和 2-酮戊二酸作为辅助因子和辅助底物。在这里，我们研究了 AlkB 蛋白对 3-甲基胸腺嘧啶 (3-meT) 和 1-甲基鸟嘌呤 (1-meG) 的活性，这两个小损伤在结构上类似于 1-meA 和 3-meC。 AlkB 以及人类 AlkB 同源物 hABH2 和 hABH3 都能够使含有单个 3-meT 残基的 DNA 寡核苷酸中的 3-meT 去甲基化。此外，由 tRNA 化学甲基化引入的 1-meG 损伤也能被 AlkB 有效去除。与 1-meA 和 3-meC 不同，对应于 1-meG 或 3-meT 的核苷或碱基不会刺激 2-酮戊二酸的未偶联、AlkB 介导的脱羧作用。我们的数据显示3-meT和1-meG被AlkB修复，但表明这些底物的识别与1-meA和3-meC的情况不同。
The Escherichia coli AlkB protein repairs 1-methyladenine (1-meA) and 3-methylcytosine (3-meC) lesions in DNA and RNA by oxidative demethylation, a reaction requiring ferrous iron and 2-oxoglutarate as cofactor and co-substrate, respectively. Here, we have studied the activity of AlkB proteins on 3-methylthymine (3-meT) and 1-methylguanine (1-meG), two minor lesions which are structurally analogous to 1-meA and 3-meC. AlkB as well as the human AlkB homologues, hABH2 and hABH3, were all able to demethylate 3-meT in a DNA oligonucleotide containing a single 3-meT residue. Also, 1-meG lesions introduced by chemical methylation of tRNA were efficiently removed by AlkB. Unlike 1-meA and 3-meC, nucleosides or bases corresponding to 1-meG or 3-meT did not stimulate the uncoupled, AlkB-mediated decarboxylation of 2-oxoglutarate. Our data show that 3-meT and 1-meG are repaired by AlkB, but indicate that the recognition of these substrates is different from that in the case of 1-meA and 3-meC.