Document Type
Article
Date of Original Version
5-22-2019
Department
Biomedical and Pharmaceutical Sciences
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 α-ketoglutarate (α-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 α-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 syn-conformation, 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.
Citation/Publisher Attribution
Ke Bian, Stefan A P Lenz, Qi Tang, Fangyi Chen, Rui Qi, Marco Jost, Catherine L Drennan, John M Essigmann, Stacey D Wetmore, Deyu Li, DNA repair enzymes ALKBH2, ALKBH3, and AlkB oxidize 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine in vitro, Nucleic Acids Research, Volume 47, Issue 11, 20 June 2019, Pages 5522–5529, https://doi.org/10.1093/nar/gkz395
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License