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Review

Nature Reviews Molecular Cell Biology 5, 148–157 (1 February 2004) | doi:10.1038/nrm1312

Repairing DNA-methylation damage

Barbara Sedgwick

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.