Direct decarboxylation of 5-carboxylcytosine by DNA C5-methyltransferases.
S-Adenosylmethionine-dependent DNA methyltransferases (MTases) perform direct methylation of cytosine to yield 5-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.
Department of Biological DNA Modification, Institute of Biotechnology, Vilnius University , 02241 Vilnius, Lithuania.
Zita
Z
Liutkevičiūtė
Edita
E
Kriukienė
Janina
J
Ličytė
Milda
M
Rudytė
Giedrė
G
Urbanavičiūtė
Saulius
S
Klimašauskas
D000818:Animals; D001419:Bacteria / Q000201:enzymology; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism*; D003653:Decarboxylation; D006801:Humans; D051379:Mice
C560974:5-carboxylcytosine; D003596:Cytosine; D004248:DNA (Cytosine-5-)-Methyltransferases