AlkB-mediated oxidative demethylation reverses DNA damage in Escherichia coli
AlkB-mediated oxidative demethylation reverses DNA damage in Escherichia coli
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DOI：
10.1038/nature01048
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发表时间：
2002-09-12
期刊：
影响因子：
64.8
通讯作者：
Seeberg, E
中科院分区：
文献类型：
--
作者：
Falnes, PO;Johansen, RF;Seeberg, E
已知细菌AlkB蛋白参与烷基化损伤后的细胞恢复；然而，这种蛋白的功能仍然未知。已经在包括人类在内的几种生物中发现了AlkB同源物，最近的一项序列比对研究表明，这些蛋白可能属于2-氧丙二酸依赖和铁依赖加氧酶（ogg - fe (II)-加氧酶）的超家族(1)。本研究表明，来自大肠杆菌的AlkB确实是一种2-氧戊二酸依赖和铁依赖的DNA修复酶，它通过1-甲基腺嘌呤残基的氧化去甲基化机制释放烷基化DNA中的复制块。这一机制代表了DNA修复的新途径，是目前发现的第三种DNA损伤逆转机制。
The bacterial AlkB protein is known to be involved in cellular recovery from alkylation damage; however, the function of this protein remains unknown. AlkB homologues have been identified in several organisms, including humans, and a recent sequence alignment study has suggested that these proteins may belong to a superfamily of 2-oxoglutarate-dependent and iron-dependent oxygenases (2OG-Fe(II)-oxygenases)(1). Here we show that AlkB from Escherichia coli is indeed a 2-oxoglutarate-dependent and iron-dependent DNA repair enzyme that releases replication blocks in alkylated DNA by a mechanism involving oxidative demethylation of 1-methyladenine residues. This mechanism represents a new pathway for DNA repair and the third type of DNA damage reversal mechanism so far discovered.