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PMID: 22327402 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Nature chemical biology ·Vol. 8 ·No. 4 ·2012-02-12 ·Pages 328-30

Zhang L, Lu X, Lu J, Liang H, Dai Q, Xu GL, Luo C, Jiang H, He C

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.

MeSH Terms
Catalytic Domain Crystallography, X-Ray Cytosine/analogs & derivatives,chemistry DNA/chemistry,metabolism DNA Methylation Humans Models, Molecular Protein Conformation Thymine DNA Glycosylase/chemistry,metabolism
Chemicals
5-carboxylcytosine Cytosine DNA Thymine DNA Glycosylase
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Zhang Liang
Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois, USA.
Lu Xingyu
Lu Junyan
Liang Haihua
Dai Qing
Xu Guo-Liang
Luo Cheng
Jiang Hualiang
He Chuan
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Article Info
Journal
Nature chemical biology
Abbr.
Nat Chem Biol
ISSN
1552-4469
DOI
10.1038/nchembio.914
Published
2012-02-12
Epub
2012-00-12
Pages
328-30
Language
English
Region
United States
NLM ID
101231976
PMCID
PMC3307914
Subset
IM
Grants
NHGRI NIH HHS · K01 HG006699 · United States
NIGMS NIH HHS · R01 GM071440 · United States
NIGMS NIH HHS · R01 GM071440-08 · United States
NIGMS NIH HHS · GM071440 · United States
Databases
PDB
3UO7, 3UOB
External Links
PubMed source DOI: 10.1038/nchembio.914 PMC Full Text View journal details
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