AlkB proteins are dioxygenases that repair alkylation damage to DNA and RNA []. 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 [].Nine mammalian AlkB homologues exist (ALKBH1-8, FTO), but only a subset functions as DNA/RNA repair enzymes [], 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 [].
