1. Centre for Molecular Biology and Neuroscience, and Institute of Medical Microbiology, University of Oslo, National Hospital, 0027 Oslo, Norway

Correspondence to: Pål Ø. Falnes Correspondence and requests for materials should be addressed to P.Ø.F. (e-mail: Email: pal.falnes@labmed.uio.no).

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.