Yokochi Tomoki, Robertson Keith D
Epigenetic Gene Regulation and Cancer Section, Laboratory of Receptor Biology and Gene Expression, Bldg.41, Room B715, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Bioorg Chem. 2004 Aug;32(4):234-43. doi: 10.1016/j.bioorg.2004.04.005.
Mammalian DNA methyltransferase Dnmt3a is required for de novo methylation of CpG dinucleotides in genomic DNA. While DNA methyltransferase inhibitors have been extensively utilized both in vitro and in vivo, no stimulator of catalytic activity has been identified thus far. Here we show that the methyltransfer activity of Dnmt3a is stimulated by the addition of dimethyl sulfoxide (DMSO) to the reaction solution in vitro. Enzymatic analysis of initial reaction velocity suggests that the DMSO stimulation effect depends on the interaction between DMSO and the reaction substrates (DNA and AdoMet), but not the enzyme itself.
哺乳动物DNA甲基转移酶Dnmt3a是基因组DNA中CpG二核苷酸从头甲基化所必需的。虽然DNA甲基转移酶抑制剂已在体外和体内广泛应用,但迄今为止尚未发现催化活性的刺激剂。在这里,我们表明,在体外反应溶液中添加二甲基亚砜(DMSO)可刺激Dnmt3a的甲基转移活性。对初始反应速度的酶促分析表明,DMSO刺激效应取决于DMSO与反应底物(DNA和腺苷甲硫氨酸)之间的相互作用,而不是酶本身。