Journal
CHEMISTRY-A EUROPEAN JOURNAL
Volume 27, Issue 31, Pages 8100-8104Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/chem.202100551
Keywords
DNA repair; DNA modification; epigenetics; mass spectrometry; oxidative lesion
Categories
Funding
- Deutsche Forschungsgemeinschaft (DFG) [GRK2338, 321812289, CRC1309, 325871075, CRC1361, 893547839]
- European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme [741912]
- Marie Skodowska-Curie grant [765266]
- Volkswagen Foundation
- Projekt DEAL
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The four non-canonical nucleotides in the human genome, along with oxidized nucleotides formed by Tet enzymes, contribute to epigenetic regulation of gene expression. Experimental evidence for the presence of these oxidized nucleotides in fungi and plants is unclear, necessitating further research for clarification in these organisms.
The four non-canonical nucleotides in the human genome 5-methyl-, 5-hydroxymethyl-, 5-formyl- and 5-carboxydeoxycytidine (mdC, hmdC, fdC and cadC) form a second layer of epigenetic information that contributes to the regulation of gene expression. Formation of the oxidized nucleotides hmdC, fdC and cadC requires oxidation of mdC by ten-eleven translocation (Tet) enzymes that require oxygen, Fe(II) and alpha-ketoglutarate as cosubstrates. Although these oxidized forms of mdC are widespread in mammalian genomes, experimental evidence for their presence in fungi and plants is ambiguous. This vagueness is caused by the fact that these oxidized mdC derivatives are also formed as oxidative lesions, resulting in unclear basal levels that are likely to have no epigenetic function. Here, we report the xdC levels in the fungus Amanita muscaria in comparison to murine embryonic stem cells (mESCs), HEK cells and induced pluripotent stem cells (iPSCs), to obtain information about the basal levels of hmdC, fdC and cadC as DNA lesions in the genome.
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