Cytosine-5-methyltransferases add aldehydes to DNA

被引:107
作者
Liutkeviciute, Zita [1 ]
Lukinavicius, Grazvydas [1 ]
Masevicius, Viktoras [1 ,2 ]
Daujotyte, Dalia [1 ]
Klimasauskas, Saulius [1 ]
机构
[1] Inst Biotechnol, Lab Biol DNA Modificat, Vilnius, Lithuania
[2] Vilnius State Univ, Dept Chem, Vilnius, Lithuania
关键词
METHYLTRANSFERASE; FORMALDEHYDE; 5-METHYLCYTOSINE; DEMETHYLATION; METHYLATION; DEAMINATION; MECHANISM; ENZYMES; HELIX; BASE;
D O I
10.1038/nchembio.172
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-alpha-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.
引用
收藏
页码:400 / 402
页数:3
相关论文
共 26 条
[1]   Catalytic promiscuity in biocatalysis: Using old enzymes to form new bonds and follow new pathways [J].
Bornscheuer, UT ;
Kazlauskas, RJ .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2004, 43 (45) :6032-6040
[2]   Sequence-structure-function studies of tRNA:m5C methyltransferase Trm4p and its relationship to DNA:m5C and RNA:m5U methyltransferases [J].
Bujnicki, JM ;
Feder, M ;
Ayres, CL ;
Redman, KL .
NUCLEIC ACIDS RESEARCH, 2004, 32 (08) :2453-2463
[3]   AdoMet-dependent methylation, DNA methyltransferases and base flipping [J].
Cheng, XD ;
Roberts, RJ .
NUCLEIC ACIDS RESEARCH, 2001, 29 (18) :3784-3795
[4]   One-pot synthesis of triazole-linked glycoconjugates [J].
Chittaboina, S ;
Xie, F ;
Wang, Q .
TETRAHEDRON LETTERS, 2005, 46 (13) :2331-2336
[5]   Chemical mapping of cytosines enzymatically flipped out of the DNA helix [J].
Daujotyte, Dalia ;
Liutkeviciute, Zita ;
Tamulaitis, Gintautas ;
Klimasauskas, Saulius .
NUCLEIC ACIDS RESEARCH, 2008, 36 (10)
[6]   Eukaryotic cytosine methyltransferases [J].
Goll, MG ;
Bestor, TH .
ANNUAL REVIEW OF BIOCHEMISTRY, 2005, 74 :481-514
[7]   HYPERMODIFIED BASES IN DNA [J].
GOMMERSAMPT, JH ;
BORST, P .
FASEB JOURNAL, 1995, 9 (11) :1034-1042
[8]   ROLES OF CYS148 AND ASP179 IN CATALYSIS BY DEOXYCYTIDYLATE HYDROXYMETHYLASE FROM BACTERIOPHAGE-T4 EXAMINED BY SITE-DIRECTED MUTAGENESIS [J].
GRAVES, KL ;
BUTLER, MM ;
HARDY, LW .
BIOCHEMISTRY, 1992, 31 (42) :10315-10321
[9]   On the mechanism of demethylation of 5-methylcytosine in DNA [J].
Hamm, Stefan ;
Just, George ;
Lacoste, Nathalie ;
Moitessier, Nicolas ;
Szyf, Moshe ;
Mamer, Orval .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (03) :1046-1049
[10]   The implausibility of leukemia induction by formaldehyde: a critical review of the biological evidence on distant-site toxicity [J].
Heck, HD ;
Casanova, M .
REGULATORY TOXICOLOGY AND PHARMACOLOGY, 2004, 40 (02) :92-106