Thymine DNA glycosylase specifically recognizes 5-carboxylcytosine-modified DNA

  • Nat Chem Biol. 2012 Feb 12;8(4):328-30. doi: 10.1038/nchembio.914.
Liang Zhang  1 ,  Xingyu Lu ,  Junyan Lu ,  Haihua Liang ,  Qing Dai ,  Guo-Liang Xu ,  Cheng Luo ,  Hualiang Jiang ,  Chuan He
Affiliations
  • 1. Department of Chemistry and Institute for Biophysical Dynamics, The University of Chicago, Chicago, Illinois, USA.
PMID: 22327402 DOI: 10.1038/nchembio.914
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.