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

Publication Type:

Journal Article


Nat Chem Biol, Volume 8, Issue 4, p.328-30 (2012)


Catalytic Domain, Crystallography, X-Ray, Cytosine, DNA, DNA Methylation, Humans, Models, Molecular, Protein Conformation, Thymine DNA Glycosylase


<p>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.</p>