Liutkeviciute Zita, Lukinavicius Grazvydas, Masevicius Viktoras, Daujotyte Dalia, Klimasauskas Saulius
Laboratory of Biological DNA Modification, Institute of Biotechnology, Vilnius, Lithuania.
Nat Chem Biol. 2009 Jun;5(6):400-2. doi: 10.1038/nchembio.172.
Targeted methylation of cytosine residues by S-adenosylmethionine-dependent DNA methyltransferases modulates gene expression in vertebrates. Here we show that cytosine-5-methyltransferases catalyze reversible covalent addition of exogenous aliphatic aldehydes to their target residues in DNA, thus yielding corresponding 5-hydroxyalkylcytosines. Such atypical enzymatic reactions with non-cofactor-like substrates open new ways for sequence-specific derivatization of DNA and demonstrate enzymatic exchange of 5-hydroxymethyl groups on cytosine in support of an oxidative mechanism of DNA demethylation.
依赖S-腺苷甲硫氨酸的DNA甲基转移酶对胞嘧啶残基进行靶向甲基化，可调节脊椎动物的基因表达。在此，我们表明胞嘧啶-5-甲基转移酶催化外源性脂肪醛可逆共价加成到其在DNA中的靶残基上，从而产生相应的5-羟烷基胞嘧啶。这种与非辅因子样底物的非典型酶促反应为DNA的序列特异性衍生化开辟了新途径，并证明了胞嘧啶上5-羟甲基的酶促交换，支持DNA去甲基化的氧化机制。
