Ethylation of poly(dC-dG).poly(dC-dG) by ethyl methanesulfonate stimulates the activity of mammalian DNA methyltransferase in vitro.

Ethylation of poly(dC-dG).poly(dC-dG) by ethyl methanesulfonate stimulates the activity of mammalian DNA methyltransferase in vitro.
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甲磺酸乙酯对聚 (dC-dG).聚 (dC-dG) 的乙基化可在体外刺激哺乳动物 DNA 甲基转移酶的活性。

DOI:
10.1073/pnas.82.4.1045
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发表时间:
1985
影响因子:
11.1
通讯作者:
Ivarie,R
Ivarie,R
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Farrance,IK;Ivarie,R

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聚(dC-dG).聚(dC-dG)与已知致癌物甲磺酸乙酯(EtMes)的乙基化,在EtMes/C X G碱基对摩尔比不断增加的情况下,在体外甲基化过程中,通过部分纯化的大鼠DNA(cytosine-5)-甲基转移酶(EC 2.1.1.37)逐渐刺激DNA的甲基接受能力。当2.7%的鸟嘌呤在N-7位(DNA中EtMes乙基化的主要位点)被修饰时,最大刺激是模拟处理的DNA的2倍。如果在鸟嘌呤N-7处的CpG位点“半甲基化”模拟半甲基化的CpG位点,我们计算出该酶对半甲基化的CpG的相对亲和力是未修饰的CpG的18倍。如果磷酸二酯键的二氧磷酸氧的乙基化是刺激的原因,则相对亲和力可能高得多,高达370倍。
Ethylation of poly(dC-dG).poly(dC-dG) with ethyl methanesulfonate (EtMes), a known carcinogen, at increasing molar ratios of EtMes/C X G base pairs progressively stimulated the methyl-accepting ability of the DNA during in vitro methylation by partially purified rat DNA (cytosine-5)-methyltransferase (EC 2.1.1.37). Maximum stimulation was 2-fold over mock-treated DNA when 2.7% of the guanines were modified at the N-7 position, the major site of ethylation by EtMes in DNA. If a CpG site "hemiethylated" at guanine N-7 mimics a hemimethylated CpG site, we calculate that the enzyme has a relative affinity for hemiethylated CpG 18-fold above unmodified CpG. If ethylation of a dioxyphosphate oxygen of the phosphodiester bond is responsible for stimulation, the relative affinity could be much higher, up to 370-fold.