| dc.description.abstract | Abstract E. coli AlkB protein was discovered three decades ago and is known to be involved in direct damage reversal of methylation lesions in DNA and RNA through oxidative demethylation. The protein belongs to the superfamily of 2-oxoglutarate and Fe(II)-dependent dioxygenases. Nine mammalian homologs of AlkB, ALKBH1-8 and FTO have been identified. In vitro repair activity, or other nucleic acid modification activity, has been reported for some of the mammalian homologs, while at least one homolog has been shown to have a protein substrate. The function is still unknown or disputed for several of the mammalian AlkB homologs. In this study, a set of nearly 200 metazoan high quality AlkB homolog sequences has been collected and carefully analyzed. The present work for the first time presented a detailed, extensive and reliable phylogeny for the AlkB homologs in vertebrates and other metazoans. It shows that the gene duplications resulting in eight mammalian paralogs are ancient and occurred in a common ancestor of all metazoans. Structural and sequence data for the AlkB homologs have been analyzed in order to help unravel the function of these enzymes. The enzymatic activity of AlkB homologs in metazoans, except human and mouse has not previously been studied. In this study, In vitro and in vivo repair activities of AlkB homologs from selected invertebrates are shown. Keywords/phrases: 2OG and Fe(II)-dependent dioxygenases, phylogeny, AlkB homologs, enzymatic demethylation/decarboxylation, structural mapping, homology modelling, functional complementation. | eng |