Thymine DNA glycosylase specifically recognizes 5-carboxylcytosine-modified DNA

• DOI: 10.1038/nchembio.914
• Publication Date: 2012-02-12T18:52:20Z
• Authors: Liang Zhang; Xingyu Lu; Junyan Lu; Haihua Liang; Qing Dai; Guo-Liang Xu; Cheng Luo; Hualiang Jiang; Chuan He
• Keywords: 5-Methylcytosine; Cytosine; DNA demethylation; Thymine; Demethylation

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.