Oxidized C5-methyl cytosine bases in DNA: 5-Hydroxymethylcytosine; 5-formylcytosine; and 5-carboxycytosine

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Recent reports suggest that the Tet enzyme family catalytically oxidize 5-methylcytosine in mammalian cells. The oxidation of 5-methylcytosine can result in three chemically distinct species – 5-hydroxymethylcytsine, 5-formylcytosine, and 5-carboxycytosine. While the base excision repair machinery processes 5-formylcytosine and 5-carboxycytosine rapidly, 5-hydroxymethylcytosine is stable under physiological conditions. As a stable modification 5-hydroxymethylcytosine has a broad range of functions, from stem cell pluriopotency to tumorigenesis. The subsequent oxidation products, 5-formylcytosine and 5-carboxycytosine, are suggested to be involved in an active DNA demethylation pathway. This review provides an overview of the biochemistry and biology of 5-methylcytosine oxidation products.

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