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

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.

SUBMITTER: Zhang L

PROVIDER: S-EPMC3307914 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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

Zhang Liang L Lu Xingyu X Lu Junyan J Liang Haihua H Dai Qing Q Xu Guo-Liang GL Luo Cheng C Jiang Hualiang H He Chuan C

Nature chemical biology 20120212 4

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 t ...[more]

PMID: 22327402

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