DNA repair enzymes ALKBH2, ALKBH3, and AlkB oxidize 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine in vitro
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gkz395.pdf
Description
Published version
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1.78 MB
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Author(s)
Bian, Ke
Lenz, Stefan A P
Tang, Qi
Chen, Fangyi
Qi, Rui
Jost, Marco
Drennan, Catherine L
Essigmann, John M
Wetmore, Stacey D
Li, Deyu
Date Issued
May 2019
Journal
Nucleic Acids Research
Publisher
Oxford University Press (OUP)
Citation
Bian,Ke et al. "DNA repair enzymes ALKBH2, ALKBH3, and AlkB oxidize 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine in vitro." Nucleic Acids Research 47, 11 (June 2019): 5522–5529. ©2019 The Author(s).
Version
Final published version
Abstract
5-Methylcytosine (5mC) in DNA CpG islands is an important epigenetic biomarker for mammalian gene regulation. It is oxidized to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) by the ten-eleven translocation (TET) family enzymes, which are -ketoglutarate (-KG)/Fe(II)-dependent dioxygenases. In this work, we demonstrate that the epigenetic marker 5mC is modified to 5hmC, 5fC, and 5caC in vitro by another class of -KG/Fe(II)-dependent proteins-the DNA repair enzymes in the AlkB family, which include ALKBH2, ALKBH3 in huamn and AlkB in Escherichia coli. Theoretical calculations indicate that these enzymes may bind 5mC in the synconformation, placing the methyl group comparable to 3-methylcytosine, the prototypic substrate of AlkB. This is the first demonstration of the AlkB proteins to oxidize a methyl group attached to carbon, instead of nitrogen, on a DNA base. These observations suggest a broader role in epigenetics for these DNA repair proteins.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Center for Environmental Health Sciences
Massachusetts Institute of Technology. Department of Biological Engineering
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DOI of Published Version
https://doi.org/10.1093/nar/gkz395
