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. 2022 Mar 8;12(3):417. doi: 10.3390/biom12030417

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© 2022 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

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Steps for dynamic modifications of Cytosine and TET-mediated oxidation. (A) The methylation of deoxycytosine (C) residues to 5-methylcytosine (5mC) are introduced by DNA methyltransferase (DNMT) enzymes and sequentially oxidized by ten–eleven translocation (TET) enzymes via 5-hydroxymethylcytosine (5mC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). SAM, S-adenosylmethionine; SAH, S-adenosylhomocysteine; α-KG, α-ketoglutarate. (B) 5fC and 5caC are identified and excised by thymine DNA glycosylase (TDG) to produce an abasic site. The base-excision-repair (BER) pathway implicates excision of the abasic site, replacement of the nucleotide using unmodified deoxycytidine triphosphate (dCTP) by a DNA polymerase (generating pyrophosphate, PPi) and ligation to repair the nick.