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通过含2-氨基嘌呤的DNA研究CpG DNA甲基转移酶M.SssI和Dnmt3a的作用机制。

Mechanism of CpG DNA methyltransferases M.SssI and Dnmt3a studied by DNA containing 2-aminopurine.

作者信息

Cherepanova Natalia A, Minero Antonio S, Rakhimova Alina R, Gromova Elizaveta S

机构信息

Department of Chemistry, Moscow State University, Moscow, Russia.

出版信息

Nucleosides Nucleotides Nucleic Acids. 2011 Jul-Aug;30(7-8):619-31. doi: 10.1080/15257770.2011.583973.

DOI:10.1080/15257770.2011.583973
PMID:21888552
Abstract

Murine DNA methyltransferases Dnmt3a-CD and M.SssI from Spiroplasma methylate cytosines at CpG sites. The role of 6-oxo groups of guanines in DNA methylation by these enzymes has been studied using DNA substrates, which contained 2-aminopurine at different positions. Removal of the 6-oxo group of the guanine located adjacent to the target cytosine in the CpG site dramatically reduces the stability of the methyltransferase-DNA complexes and leads to a significant decrease in the methylation. Apparently, O6 of this guanine is involved in the recognition of CpG sites by the enzymes. Cooperative binding of Dnmt3a-CD to 2-aminopurine-containing DNA and the formation of nonproductive enzyme-substrate complexes were observed.

摘要

小鼠DNA甲基转移酶Dnmt3a-CD和来自螺原体的M.SssI在CpG位点使胞嘧啶甲基化。使用在不同位置含有2-氨基嘌呤的DNA底物,研究了鸟嘌呤的6-氧代基团在这些酶介导的DNA甲基化中的作用。去除CpG位点中与目标胞嘧啶相邻的鸟嘌呤的6-氧代基团,会显著降低甲基转移酶-DNA复合物的稳定性,并导致甲基化显著减少。显然,该鸟嘌呤的O6参与了酶对CpG位点的识别。观察到Dnmt3a-CD与含2-氨基嘌呤的DNA的协同结合以及非生产性酶-底物复合物的形成。

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