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Nature. 2013 Oct 24;502(7472):472-9. doi: 10.1038/nature12750.

TET enzymes, TDG and the dynamics of DNA demethylation.

Author information

1
1] Department of Medicine, Raymond and Ruth Perelman School of Medicine, University of Pennsylvania, Philadelphia 19104, USA. [2] Department of Biochemistry and Biophysics, Raymond and Ruth Perelman School of Medicine, University of Pennsylvania, Philadelphia 19104, USA.

Abstract

DNA methylation has a profound impact on genome stability, transcription and development. Although enzymes that catalyse DNA methylation have been well characterized, those that are involved in methyl group removal have remained elusive, until recently. The transformative discovery that ten-eleven translocation (TET) family enzymes can oxidize 5-methylcytosine has greatly advanced our understanding of DNA demethylation. 5-Hydroxymethylcytosine is a key nexus in demethylation that can either be passively depleted through DNA replication or actively reverted to cytosine through iterative oxidation and thymine DNA glycosylase (TDG)-mediated base excision repair. Methylation, oxidation and repair now offer a model for a complete cycle of dynamic cytosine modification, with mounting evidence for its significance in the biological processes known to involve active demethylation.

PMID:
24153300
PMCID:
PMC4046508
DOI:
10.1038/nature12750
[Indexed for MEDLINE]
Free PMC Article

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