Direct Decarboxylation of 5-Carboxylcytosine by DNA C5-Methyltransferases

被引：54

作者：

Liutkeviciute, Zita ^{[1
]}

Kriukiene, Edita ^{[1
]}

Licyte, Janina ^{[1
]}

Rudyte, Milda ^{[1
]}

Urbanaviciute, Giedre ^{[1
]}

Klimasauskas, Saulius ^{[1
]}

机构：

[1] Vilnius State Univ, Dept Biol DNA Modificat, Inst Biotechnol, LT-02241 Vilnius, Lithuania

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2014年 / 136卷 / 16期

关键词：

TET PROTEINS; 5-HYDROXYMETHYLCYTOSINE; 5-FORMYLCYTOSINE; 5-METHYLCYTOSINE; MECHANISM; BASE; METHYLATION; CONVERSION; EXCISION; DNMT3B;

D O I：

10.1021/ja5019223

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

S-Adenosylmethionine-dependent DNA methyltransferases (MTases) perform direct methylation of cytosine to yield S-methylcytosine (5mC), which serves as part of the epigenetic regulation mechanism in vertebrates. Active demethylation of 5mC by TET oxygenases produces 5-formylcytosine (fC) and 5-carboxylcytosine (caC), which were shown to be enzymatically excised and then replaced with an unmodified nucleotide. Here we find that both bacterial and mammalian C5-MTases can catalyze the direct decarboxylation of caC yielding unmodified cytosine in DNA in vitro but are inert toward fC. The observed atypical enzymatic C-C bond cleavage reaction provides a plausible precedent for a direct reversal of caC to the unmodified state in DNA and offers a unique approach for sequence-specific analysis of genomic caC.

引用

页码：5884 / 5887

页数：4

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