Phylogenomic identification of five new human homologs of the DNA repair enzyme AlkB.
BACKGROUND
Combination of biochemical and bioinformatic analyses led to the discovery of oxidative demethylation - a novel DNA repair mechanism catalyzed by the Escherichia coli AlkB protein and its two human homologs, hABH2 and hABH3. This discovery was based on the prediction made by Aravind and Koonin that AlkB is a member of the 2OG-Fe2+ oxygenase superfamily.


RESULTS
In this article, we report identification and sequence analysis of five human members of the (2OG-Fe2+) oxygenase superfamily designated here as hABH4 through hABH8. These experimentally uncharacterized and poorly annotated genes were not associated with the AlkB family in any database, but are predicted here to be phylogenetically and functionally related to the AlkB family (and specifically to the lineage that groups together hABH2 and hABH3) rather than to any other oxygenase family. Our analysis reveals the history of ABH gene duplications in the evolution of vertebrate genomes.


CONCLUSIONS
We hypothesize that hABH 4-8 could either be back-up enzymes for hABH1-3 or may code for novel DNA or RNA repair activities. For example, enzymes that can dealkylate N3-methylpurines or N7-methylpurines in DNA have not been described. Our analysis will guide experimental confirmation of these novel human putative DNA repair enzymes.
Kurowski
Michal A
MA
Bioinformatics Laboratory, International Institute of Molecular and Cell Biology, Trojdena 4, 02-109 Warsaw, Poland. michal@genesilico.pl
Bhagwat
Ashok S
AS
Papaj
Grzegorz
G
Bujnicki
Janusz M
JM
D000595:Amino Acid Sequence; D004260:DNA Repair; D030541:Databases, Genetic; D015894:Genome, Human; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D010802:Phylogeny; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D006899:Mixed Function Oxygenases