Phylogenomic identification of five new human homologs of the DNA repair enzyme AlkB - PubMed (original) (raw)

Phylogenomic identification of five new human homologs of the DNA repair enzyme AlkB

Michal A Kurowski et al. BMC Genomics. 2003.

Abstract

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.

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Figures

Figure 1

Figure 1

The multiple sequence alignment of E. coli AlkB and all human members of the AlkB family described previously (ABH1-3) and in this study (ABH4-8). Residues conserved in at least 4 members of the family are highlighted in black, residues with similar physico-chemical character are highlighted in gray. The length of loops omitted for the clarity of the presentation are shown in parentheses. The N- and C-terminal residues are numbered. The predicted catalytic residues are indicated with asterisks (*).

Figure 2

Figure 2

The maximum likelihood phylogenetic tree of the AlkB family. Only representative members (from human and E. coli), corresponding to the sequences in Fig. 1 are shown for the clarity of presentation. The position of the root was inferred from the large 2OG-Fe2+ oxygenase superfamily tree (data not shown). The topology of the presented tree received very high p-value support according to the Shimodaira-Hasegawa [31] and "approximately unbiased" [32] tests (0.998 and 0.988, respectively).

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References

    1. Hegg EL, Que L., Jr The 2-His-1-carboxylate facial triad – an emerging structural motif in mononuclear non-heme iron(II) enzymes. Eur J Biochem. 1997;250:625–629. - PubMed
    1. Roach PL, Clifton IJ, Fulop V, Harlos K, Barton GJ, Hajdu J, Andersson I, Schofield CJ, Baldwin JE. Crystal structure of isopenicillin N synthase is the first from a new structural family of enzymes. Nature. 1995;375:700–704. doi: 10.1038/375700a0. - DOI - PubMed
    1. Aravind L, Koonin EV. The DNA-repair protein AlkB, EGL-9, and leprecan define new families of 2-oxoglutarate- and iron-dependent dioxygenases. Genome Biol. 2001;2:RESEARCH0007. doi: 10.1186/gb-2001-2-3-research0007. - DOI - PMC - PubMed
    1. Trewick SC, Henshaw TF, Hausinger RP, Lindahl T, Sedgwick B. Oxidative demethylation by Escherichia coli AlkB directly reverts DNA base damage. Nature. 2002;419:174–178. doi: 10.1038/nature00908. - DOI - PubMed
    1. Falnes PO, Johansen RF, Seeberg E. AlkB-mediated oxidative demethylation reverses DNA damage in Escherichia coli. Nature. 2002;419:178–182. doi: 10.1038/nature01048. - DOI - PubMed

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