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). 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenine / analogs & derivatives*
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Adenine / metabolism
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Alkylation
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Base Sequence
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Chromatography, High Pressure Liquid
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DNA Damage*
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DNA Methylation*
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DNA Repair*
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DNA Replication
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DNA, Bacterial / genetics
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DNA, Bacterial / metabolism*
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DNA, Single-Stranded / genetics
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DNA, Single-Stranded / metabolism
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Escherichia coli / enzymology
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Escherichia coli / genetics*
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Escherichia coli / metabolism*
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Escherichia coli Proteins / genetics
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Escherichia coli Proteins / metabolism*
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Formaldehyde / metabolism
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Mixed Function Oxygenases / genetics
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Mixed Function Oxygenases / metabolism*
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Oxidation-Reduction
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Transformation, Bacterial
Substances
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DNA, Bacterial
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DNA, Single-Stranded
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Escherichia coli Proteins
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Formaldehyde
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1-methyladenine
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Mixed Function Oxygenases
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AlkB protein, E coli
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Adenine