1. Institute of Cancer Research and Molecular Biology, Norwegian University of Science and Technology, N-7489 Trondheim, Norway
2. Centre of Molecular Biology and Neuroscience, and Institute of Medical Microbiology, University of Oslo, The National Hospital, N-0027 Oslo, Norway
3. These authors contributed equally to this work

Correspondence to: Hans E. Krokan¹ Correspondence and requests for materials should be addressed to H.E.K. (e-mail: Email: hans.krokan@medisin.ntnu.no).

Abstract

Repair of DNA damage is essential for maintaining genome integrity, and repair deficiencies in mammals are associated with cancer, neurological disease and developmental defects¹. Alkylation damage in DNA is repaired by at least three different mechanisms, including damage reversal by oxidative demethylation of 1-methyladenine and 3-methylcytosine by Escherichia coli AlkB^{2, 3}. By contrast, little is known about consequences and cellular handling of alkylation damage to RNA⁴. Here we show that two human AlkB homologues, hABH2 and hABH3, also are oxidative DNA demethylases and that AlkB and hABH3, but not hABH2, also repair RNA. Whereas AlkB and hABH3 prefer single-stranded nucleic acids, hABH2 acts more efficiently on double-stranded DNA. In addition, AlkB and hABH3 expressed in E. coli reactivate methylated RNA bacteriophage MS2 in vivo, illustrating the biological relevance of this repair activity and establishing RNA repair as a potentially important defence mechanism in living cells. The different catalytic properties and the different subnuclear localization patterns shown by the human homologues indicate that hABH2 and hABH3 have distinct roles in the cellular response to alkylation damage.

1. Institute of Cancer Research and Molecular Biology, Norwegian University of Science and Technology, N-7489 Trondheim, Norway
2. Centre of Molecular Biology and Neuroscience, and Institute of Medical Microbiology, University of Oslo, The National Hospital, N-0027 Oslo, Norway
3. These authors contributed equally to this work

Correspondence to: Hans E. Krokan¹ Correspondence and requests for materials should be addressed to H.E.K. (e-mail: Email: hans.krokan@medisin.ntnu.no).