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Nat Chem Biol. 2012 Feb 12;8(4):328-30. doi: 10.1038/nchembio.914.

Thymine DNA glycosylase specifically recognizes 5-carboxylcytosine-modified DNA.

Author information

1
Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois, USA.

Abstract

Human thymine DNA glycosylase (hTDG) efficiently excises 5-carboxylcytosine (5caC), a key oxidation product of 5-methylcytosine in genomic DNA, in a recently discovered cytosine demethylation pathway. We present here the crystal structures of the hTDG catalytic domain in complex with duplex DNA containing either 5caC or a fluorinated analog. These structures, together with biochemical and computational analyses, reveal that 5caC is specifically recognized in the active site of hTDG, supporting the role of TDG in mammalian 5-methylcytosine demethylation.

PMID:
22327402
PMCID:
PMC3307914
DOI:
10.1038/nchembio.914
[Indexed for MEDLINE]
Free PMC Article

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