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

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• 作者：Guifang Jia ; Cai-Guang Yang ; Shangdong Yang ; Xing Jian ; Chengqi Yi ; Zhiqiang Zhou ; Chuan He
• 关键词：DNA/RNA repair ; FTO ; Oxidative demethylation
• 刊名：FEBS Letters
• 出版年：2008
• 出版时间：15 October 2008
• 年：2008
• 卷：582
• 期：23-24
• 页码：3313-3319
• 全文大小：550 K

文摘

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), ;1;-ketoglutarate (;1;-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.