修复DNA甲基化损伤。

Repairing DNA-methylation damage.

作者信息

Sedgwick Barbara

机构信息

Cancer Research UK London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, Hertfordshire EN6 3LD, UK.

出版信息

Nat Rev Mol Cell Biol. 2004 Feb;5(2):148-57. doi: 10.1038/nrm1312.

DOI:10.1038/nrm1312

PMID:15040447

Abstract

Methylating agents modify DNA at many different sites, thereby producing lethal and mutagenic lesions. To remove all the main harmful base lesions, at least three types of DNA-repair activities can be used, each of which involves a different reaction mechanism. These activities include DNA-glycosylases, DNA-methyltransferases and the recently characterized DNA-dioxygenases. The Escherichia coli AlkB dioxygenase and the two human homologues, ABH2 and ABH3, represent a novel mechanism of DNA repair. They use iron-oxo intermediates to oxidize stable methylated bases in DNA and directly revert them to the unmodified form.

摘要

甲基化试剂会在许多不同位点修饰DNA，从而产生致死性和诱变性损伤。为了去除所有主要的有害碱基损伤，至少可以使用三种类型的DNA修复活性，每种活性都涉及不同的反应机制。这些活性包括DNA糖基化酶、DNA甲基转移酶和最近鉴定出的DNA双加氧酶。大肠杆菌AlkB双加氧酶以及两种人类同源物ABH2和ABH3代表了一种新的DNA修复机制。它们利用铁氧中间体氧化DNA中稳定的甲基化碱基，并直接将其还原为未修饰的形式。