All organisms have multiple DNA repair pathways to protect against alkylation-induced mutation and cell death. For nearly two decades, we have known that the Escherichia coli alkB gene product protects against cell killing by S(N)2-alkylating agents, probably through DNA repair. Despite numerous attempts, a specific DNA repair activity could not be assigned to AlkB. Now, a breakthrough in biology and biochemistry, coupled with the discovery of an in silico protein structure, has uncovered a novel direct reversal DNA repair mechanism that is catalyzed by AlkB, namely the oxidative demethylation of N1-methyladenine or N3-methylcytosine DNA lesions. This reaction occurs on both single- and double-stranded DNA, and requires AlkB-bound non-heme Fe(2+), O(2) and alpha-ketogluterate to oxidize the offending methyl group. This is followed by the release of succinate, CO(2) and formaldehyde, and the restoration of undamaged A or C in DNA.

中文翻译：

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解决了AlkB的奥秘：通过直接逆转机制将N1-甲基腺嘌呤和N3-甲基胞嘧啶加合物氧化脱甲基。

所有生物都有多种DNA修复途径，以防止烷基化诱导的突变和细胞死亡。近二十年来，我们知道大肠杆菌alkB基因产物可以防止DNA被S（N）2-烷基化试剂杀死。尽管进行了许多尝试，但无法将特定的DNA修复活性分配给AlkB。现在，生物学和生物化学领域的突破以及计算机硅蛋白结构的发现，揭示了一种由AlkB催化的新型直接逆向DNA修复机制，即N1-甲基腺嘌呤或N3-甲基胞嘧啶DNA损伤的氧化脱甲基作用。此反应发生在单链和双链DNA上，并且需要AlkB结合的非血红素Fe（2 +），O（2）和α-酮戊二酸酯来氧化有问题的甲基。