AlkB
DNA
核糖核酸
DNA修复
DNA损伤
大肠杆菌
化学
基底切除修复术
生物
碱基对
生物化学
基因
作者
Cai‐Guang Yang,Chengqi Yi,E.M. Duguid,Christopher T. Sullivan,Xing Jian,Phoebe A. Rice,Chuan He
出处
期刊:Nature
[Springer Nature]
日期:2008-04-01
卷期号:452 (7190): 961-965
被引量:235
摘要
Escherichia coli AlkB and its human homologues ABH2 and ABH3 repair DNA/RNA base lesions by using a direct oxidative dealkylation mechanism. ABH2 has the primary role of guarding mammalian genomes against 1-meA damage by repairing this lesion in double-stranded DNA (dsDNA), whereas AlkB and ABH3 preferentially repair single-stranded DNA (ssDNA) lesions and can repair damaged bases in RNA. Here we show the first crystal structures of AlkB-dsDNA and ABH2-dsDNA complexes, stabilized by a chemical cross-linking strategy. This study reveals that AlkB uses an unprecedented base-flipping mechanism to access the damaged base: it squeezes together the two bases flanking the flipped-out one to maintain the base stack, explaining the preference of AlkB for repairing ssDNA lesions over dsDNA ones. In addition, the first crystal structure of ABH2, presented here, provides a structural basis for designing inhibitors of this human DNA repair protein.
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