Abstract |
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 (alpha-KG) 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 (dsDNA). 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.
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Authors | Guifang Jia, Cai-Guang Yang, Shangdong Yang, Xing Jian, Chengqi Yi, Zhiqiang Zhou, Chuan He |
Journal | FEBS letters
(FEBS Lett)
Vol. 582
Issue 23-24
Pg. 3313-9
(Oct 15 2008)
ISSN: 0014-5793 [Print] England |
PMID | 18775698
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- DNA, Single-Stranded
- Proteins
- Recombinant Proteins
- Uracil
- 3-methyluracil
- RNA
- Mixed Function Oxygenases
- FTO protein, mouse
- Alpha-Ketoglutarate-Dependent Dioxygenase FTO
- FTO protein, human
- Oxo-Acid-Lyases
- Thymine
- 3-methylthymine
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Topics |
- Alpha-Ketoglutarate-Dependent Dioxygenase FTO
- Animals
- DNA Repair
- DNA, Single-Stranded
(chemistry, metabolism)
- Humans
- Methylation
- Mice
- Mixed Function Oxygenases
- Oxidation-Reduction
- Oxo-Acid-Lyases
(chemistry, metabolism)
- Proteins
(chemistry, metabolism)
- RNA
(metabolism)
- Recombinant Proteins
(chemistry)
- Substrate Specificity
- Thymine
(analogs & derivatives, chemistry, metabolism)
- Uracil
(analogs & derivatives, chemistry, metabolism)
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