AlkB-mediated oxidative demethylation reverses DNA damage in Escherichia coli.
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.
Falnes
Pål Ø
PØ
Centre for Molecular Biology and Neuroscience, and Institute of Medical Microbiology, University of Oslo, National Hospital, 0027 Oslo, Norway. pal.falnes@labmed.uio.no
Johansen
Rune F
RF
Seeberg
Erling
E
D000225:Adenine / Q000031:analogs & derivatives* / Q000378:metabolism; D000478:Alkylation; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage; D019175:DNA Methylation; D004260:DNA Repair; D004261:DNA Replication; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism*; D004277:DNA, Single-Stranded / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D005557:Formaldehyde / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D014169:Transformation, Bacterial
D004269:DNA, Bacterial; D004277:DNA, Single-Stranded; D029968:Escherichia coli Proteins; D005557:Formaldehyde; C008407:1-methyladenine; D006899:Mixed Function Oxygenases; C466427:AlkB protein, E coli; D000225:Adenine