Abstract
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-α-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.
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Acknowledgements
We thank S. Moréra (Laboratoire d'Enzymologie et Biochimie Structurales) and L.C. Sowers (Loma Linda University) for the gift of an hmC-containing oligonucleotide, G. Vilkaitis (Institute of Biotechnology) for a sample of mouse Dnmt1, and M. Petrusõytė (Fermentas) for M.HpaII. Thanks are due to L. Peil for HR-MS analysis of modified nucleosides, M. Krenevicõienė for NMR spectra and E. Weinhold for valuable discussions. This work was supported by grants from the Lithuanian State Science and Study Foundation and the Ministry of Education and Science of Lithuania.
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Liutkevičiūtė, Z., Lukinavičius, G., Masevičius, V. et al. Cytosine-5-methyltransferases add aldehydes to DNA. Nat Chem Biol 5, 400–402 (2009). https://doi.org/10.1038/nchembio.172
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DOI: https://doi.org/10.1038/nchembio.172
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