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

Publication Type:

Journal Article

Authors:

Zhang, Liang; Lu, Xingyu; Lu, Junyan; Liang, Haihua; Dai, Qing; Xu, Guo-Liang; Luo, Cheng; Jiang, Hualiang; He, Chuan

Source:

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

Keywords:

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

Abstract:

<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>