Cellular DNA is composed of four canonical nucleosides (dA, dC, dG and T), which form two Watson–Crick base pairs. In addition, 5-methylcytosine (mdC) may be present. The methylation of dC to mdC is known to regulate transcriptional activity. Next to these five nucleosides, the genome, particularly of stem cells, contains three additional dC derivatives, which are formed by stepwise oxidation of the methyl group of mdC with the help of Tet enzymes. These are 5-hydroxymethyl-dC (hmdC), 5-formyl-dC (fdC), and 5-carboxy-dC (cadC). It is believed that fdC and cadC are converted back into dC, which establishes an epigenetic control cycle that starts with methylation of dC to mdC, followed by oxidation and removal of fdC and cadC. While fdC was shown to undergo intragenomic deformylation to give dC directly, a similar decarboxylation of cadC was postulated but not yet observed on the genomic level. By using metabolic labelling, we show here that cadC decarboxylates in several cell types, which confirms that both fdC and cadC are nucleosides that are directly converted back to dC within the genome by C−C bond cleavage.

中文翻译：

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5-Carboxy-2'-deoxycytidine 的基因组内脱羧

细胞 DNA 由四种经典核苷（dA、dC、dG 和 T）组成，它们形成两个 Watson-Crick 碱基对。此外，可能存在 5-甲基胞嘧啶 (mdC)。已知 dC 到 mdC 的甲基化可调节转录活性。除了这五个核苷，基因组，尤其是干细胞的基因组，还包含三个额外的 dC 衍生物，它们是在 Tet 酶的帮助下通过 mdC 的甲基基团逐步氧化形成的。它们是 5-羟甲基-dC (hmdC)、5-甲酰基-dC (fdC) 和 5-羧基-dC (cadC)。人们认为 fdC 和 cadC 被转化回 dC，这建立了一个表观遗传控制循环，该循环从 dC 甲基化为 mdC 开始，然后是 fdC 和 cadC 的氧化和去除。虽然 fdC 被证明经过基因组内去甲酰化直接产生 dC，推测 cadC 有类似的脱羧作用，但尚未在基因组水平上观察到。通过使用代谢标记，我们在这里展示了 cadC 在几种细胞类型中脱羧，这证实 fdC 和 cadC 都是核苷，它们在基因组内通过 C-C 键裂解直接转化回 dC。