5‐Hydroxymethyl‐, 5‐Formyl‐ and 5‐Carboxydeoxycytidines as Oxidative Lesions and Epigenetic Marks. Issue 31 (1st May 2021)

• Record Type: Journal Article
• Authors: Schelter, Florian; Kirchner, Angie; Traube, Franziska R.; Müller, Markus; Steglich, Wolfgang; Carell, Thomas
• Is Part Of: Chemistry. Volume 27:Issue 31(2021)
• Page Start: 8100
• Page End: 8104
• Publication Date: 2021-05-01
• Subjects: DNA repair -- DNA modification -- epigenetics -- mass spectrometry -- oxidative lesion; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.202100551
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: 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 α‐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. Abstract : Exact UHPLC‐MS 2 quantifications were used to determine the oxidative lesion and epigenetically induced levels of the non‐canonical bases hmdC, fdC and cadC and of the levels of base excision repair intermediates.