Journal
FEBS LETTERS
Volume 582, Issue 23-24, Pages 3313-3319Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2008.08.019
Keywords
DNA/RNA repair; FTO; Oxidative demethylation
Funding
- National Institute of Health [GM071440]
- W.M. Keck Foundation
- Camille and Henry Dreyfus Foundation
- Research Corporation
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The human obesity susceptibility gene, FTO, encodes a protein that is homologous to the DNA repair AlkB protein. The AlkB family proteins utilize iron( II), alpha-ketoglutarate (aKG) and dioxygen to perform oxidative repair of alkylated nucleobases in DNA and RNA. We demonstrate here the oxidative demethylation of 3-methylthymine (3-meT) in single-stranded DNA (ssDNA) and 3-methyluracil (3-meU) in single-stranded RNA (ssRNA) by recombinant human FTO protein in vitro. Both human and mouse FTO proteins preferentially repair 3-meT in ssDNA over other base lesions tested. They showed negligible activities against 3-meT in double-stranded DNA (sDNA). In addition, these two proteins can catalyze the demethylation of 3-meU in ssRNA with a slightly higher efficiency over that of 3-meT in ssDNA, suggesting that methylated RNAs are the preferred substrates for FTO. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
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