InterPro domain: IPR004574

General Information

  • Identifier IPR004574
  • Description Alkylated DNA repair protein AlkB
  • Number of genes 328
  • Gene duplication stats Loading...

Abstract

AlkB proteins are dioxygenases that repair alkylation damage to DNA and RNA [ 1 ]. The Escherichia coli alkB gene product protects against cell killing by S(N)2-alkylating agents through DNA repair by a novel direct reversal DNA repair mechanism: the oxidative demethylation of N1-methyladenine or N3-methylcytosine DNA lesions. This reaction occurs on both single- and double-stranded DNA, and requires AlkB-bound non-heme Fe(2+), O(2) and alpha-ketogluterate to oxidize the offending methyl group. This is followed by the release of succinate, CO(2) and formaldehyde, and the restoration of undamaged A or C in DNA [ 2 ].

Nine mammalian AlkB homologues exist (ALKBH1-8, FTO), but only a subset functions as DNA/RNA repair enzymes [ 3 ], and only ALKBH1 is included in this entry. In humans, ALKBH1 (ABH1) is responsible for the conversion of 5-methylcytosine to 5-formylcytosine (f5C) in position 34 in mitochondrial tRNAMet [ 4 ].


1. Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA. Nature 421, 859-63
2. AlkB mystery solved: oxidative demethylation of N1-methyladenine and N3-methylcytosine adducts by a direct reversal mechanism. Trends Biochem. Sci. 28, 2-5
3. The AlkB Family of Fe(II)/α-Ketoglutarate-dependent Dioxygenases: Repairing Nucleic Acid Alkylation Damage and Beyond. J. Biol. Chem. 290, 20734-42
4. Dealing with an Unconventional Genetic Code in  Mitochondria: The Biogenesis and Pathogenic  Defects of the 5-Formylcytosine Modification in  Mitochondrial tRNAMet. Biomolecules 7

Species distribution

Gene table

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