AlkB-mediated oxidative demethylation reverses DNA damage in Escherichia coli

Pål Ø. Falnes (), Rune F. Johansen and Erling Seeberg
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Pål Ø. Falnes: University of Oslo, National Hospital
Rune F. Johansen: University of Oslo, National Hospital
Erling Seeberg: University of Oslo, National Hospital

Nature, 2002, vol. 419, issue 6903, 178-182

Abstract: Abstract 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.

Date: 2002
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DOI: 10.1038/nature01048

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