title: Non-homologous functions of the AlkB homologs.
abstract: The DNA repair enzyme AlkB was identified in E. coli more than three decades ago. Since then, nine mammalian homologs, all members of the superfamily of alpha-ketoglutarate and Fe(II)-dependent dioxygenases, have been identified (designated ALKBH1-8 and FTO). While E. coli AlkB serves as a DNA repair enzyme, only two mammalian homologs have been confirmed to repair DNA in vivo. The other mammalian homologs have remarkably diverse substrate specificities and biological functions. Substrates recognized by the different AlkB homologs comprise erroneous methyl- and etheno adducts in DNA, unique wobble uridine modifications in certain tRNAs, methylated adenines in mRNA, and methylated lysines on proteins. The phenotypes of organisms lacking or overexpressing individual AlkB homologs include obesity, severe sensitivity to inflammation, infertility, growth retardation, and multiple malformations. Here we review the present knowledge of the mammalian AlkB homologs and their implications for human disease and development.
authors.affiliation: Clinic for Diagnostics and Intervention and Institute of Medical Microbiology, Oslo University Hospital, Rikshospitalet, 0027 Oslo, Norway Department of Anesthesiology, Division of Emergencies and Critical Care, Oslo University Hospital, The Norwegian Radium Hospital, 0310 Oslo, Norway.
authors.forename: Rune
authors.initials: R
authors.lastname: Ougland
authors.affiliation: Clinic for Diagnostics and Intervention and Institute of Medical Microbiology, Oslo University Hospital, Rikshospitalet, 0027 Oslo, Norway Department of Informatics, University of Oslo, 0316 Oslo, Norway.
authors.forename: Torbjørn
authors.initials: T
authors.lastname: Rognes
authors.affiliation: Clinic for Diagnostics and Intervention and Institute of Medical Microbiology, Oslo University Hospital, Rikshospitalet, 0027 Oslo, Norway Faculty of Medicine, Institute of Basic Medical Sciences, University of Oslo, 0317 Oslo, Norway.
authors.forename: Arne
authors.initials: A
authors.lastname: Klungland
authors.affiliation: Clinic for Diagnostics and Intervention and Institute of Medical Microbiology, Oslo University Hospital, Rikshospitalet, 0027 Oslo, Norway elisabeth.larsen@bioteknologiradet.no.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Larsen
mesh_terms: D000818:Animals; D019295:Computational Biology; D019175:DNA Methylation; D004260:DNA Repair / Q000502:physiology; D049308:Dioxygenases / Q000737:chemistry* / Q000145:classification / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000145:classification / Q000378:metabolism; D006801:Humans; D007656:Ketoglutaric Acids / Q000737:chemistry*; D051379:Mice; D006899:Mixed Function Oxygenases / Q000737:chemistry* / Q000145:classification / Q000378:metabolism; D010802:Phylogeny; D011499:Protein Processing, Post-Translational; D012323:RNA Processing, Post-Transcriptional; D012343:RNA, Transfer / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity
chemical_list: D029968:Escherichia coli Proteins; D007656:Ketoglutaric Acids; D012343:RNA, Transfer; D006899:Mixed Function Oxygenases; D049308:Dioxygenases; C466427:AlkB protein, E coli
keywords: ALKBH; AlkB homologs; DNA repair; RNA repair; epigenetics; histone demethylation; tRNA modification