Nature Chemical Biology. Human Thymine DNA glycosylase specifically recognizes 5-carboxylcytosine-modified DNA

hTDG Thymine DNA glycosylase 5-carboxylcytosine modified DNA ncb nature chemical biology cover proposal 3dc
hTDG Thymine DNA glycosylase bound to 5 carboxylcytosine modified DNA ncb Nature Chemical Biology cover proposal

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.

Nature Chemical Biology cover proposal.
Liang Zhang, Xingyu Lu, Junyan Lu, Haihua Liang, Qing Dai, Guo-Liang Xu, Cheng Luo, Hualiang Jiang & Chuan He.
Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois, USA.

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