Reversal of DNA alkylation damage by two human dioxygenases.
Article Details
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Duncan T, Trewick SC, Koivisto P, Bates PA, Lindahl T, Sedgwick B
Reversal of DNA alkylation damage by two human dioxygenases.
Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16660-5. Epub 2002 Dec 16.
- PubMed ID
- 12486230 [ View in PubMed]
- Abstract
The Escherichia coli AlkB protein protects against the cytotoxicity of methylating agents by repair of the DNA lesions 1-methyladenine and 3-methylcytosine, which are generated in single-stranded stretches of DNA. AlkB is an alpha-ketoglutarate- and Fe(II)-dependent dioxygenase that oxidizes the relevant methyl groups and releases them as formaldehyde. Here, we identify two human AlkB homologs, ABH2 and ABH3, by sequence and fold similarity, functional assays, and complementation of the E. coli alkB mutant phenotype. The levels of their mRNAs do not appear to correlate with cell proliferation but tissue distributions are different. Both enzymes remove 1-methyladenine and 3-methylcytosine from methylated polynucleotides in an alpha-ketoglutarate-dependent reaction, and act by direct damage reversal with the regeneration of the unsubstituted bases. AlkB, ABH2, and ABH3 can also repair 1-ethyladenine residues in DNA with the release of acetaldehyde.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Ascorbic acid Alpha-ketoglutarate-dependent dioxygenase alkB homolog 2 Protein Humans UnknownActivatorDetails Ascorbic acid Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3 Protein Humans UnknownActivatorDetails - Polypeptides
Name UniProt ID DNA oxidative demethylase ALKBH2 Q6NS38 Details Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3 Q96Q83 Details