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

Oxidative demethylation of 3-methylthymine and 3-methyluracil in single-stranded DNA and RNA by mouse and human FTO.
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通过小鼠和人 FTO 对单链 DNA 和 RNA 中的 3-甲基胸腺嘧啶和 3-甲基尿嘧啶进行氧化去甲基化。

DOI:
10.1016/j.febslet.2008.08.019
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发表时间:
2008-10-15
期刊:
影响因子:
3.5
通讯作者:
He, Chuan
He, Chuan
中科院分区:
生物学3区
文献类型:
--
作者:
Jia, Guifang;Yang, Cai-Guang;Yang, Shangdong;Jian, Xing;Yi, Chengqi;Zhou, Zhiqiang;He, Chuan

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人类肥胖易感基因FTO编码一种与DNA修复蛋白AlkB同源的蛋白质。AlkB家族蛋白利用铁(II)、α-酮戊二酸(α-KG)和双氧对DNA和RNA中的烷基化核碱基进行氧化修复。我们在体外用重组人FTO蛋白证明了单链DNA (ssDNA)中的3-甲基胸腺嘧啶(3-meT)和单链RNA (ssRNA)中的3-甲基尿嘧啶(3-meU)的氧化去甲基化。人和小鼠FTO蛋白都优先修复ssDNA中的3-meT,而不是其他碱基损伤。它们对双链DNA (dsDNA)中的3-meT的活性可以忽略不计。此外,这两种蛋白可以催化ssRNA中3-meU的去甲基化,其效率略高于ssDNA中3-meT的去甲基化,表明甲基化的rna是FTO的首选底物。
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), α-ketoglutarate (α-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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