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Oxidative demethylation of 3-methylthymine and 3-methyluracil in single-stranded DNA and RNA by mouse and human FTO.

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.
AuthorsGuifang Jia, Cai-Guang Yang, Shangdong Yang, Xing Jian, Chengqi Yi, Zhiqiang Zhou, Chuan He
JournalFEBS letters (FEBS Lett) Vol. 582 Issue 23-24 Pg. 3313-9 (Oct 15 2008) ISSN: 0014-5793 [Print] England
PMID18775698 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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
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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