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

被引：350

作者：

Jia, Guifang ^{[1
,2
]}

Yang, Cai-Guang ^{[1
]}

Yang, Shangdong ^{[1
]}

Jian, Xing ^{[1
]}

Yi, Chengqi ^{[1
]}

Zhou, Zhiqiang ^{[2
]}

He, Chuan ^{[1
]}

机构：

[1] Univ Chicago, Dept Chem, Chicago, IL 60637 USA

[2] China Agr Univ, Dept Appl Chem, Beijing 100094, Peoples R China

来源：

FEBS LETTERS | 2008年 / 582卷 / 23-24期

关键词：

DNA/RNA repair; FTO; Oxidative demethylation;

D O I：

10.1016/j.febslet.2008.08.019

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：3313 / 3319

页数：7

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