Thymine DNA glycosylase specifically recognizes 5-carboxylcytosine-modified DNA

Nat Chem Biol. 2012 Feb 12;8(4):328-30. 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalytic Domain
  • Crystallography, X-Ray
  • Cytosine / analogs & derivatives*
  • Cytosine / chemistry
  • DNA / chemistry
  • DNA / metabolism*
  • DNA Methylation
  • Humans
  • Models, Molecular
  • Protein Conformation
  • Thymine DNA Glycosylase / chemistry*
  • Thymine DNA Glycosylase / metabolism*

Substances

  • 5-carboxylcytosine
  • Cytosine
  • DNA
  • Thymine DNA Glycosylase

Associated data

  • PDB/3UO7
  • PDB/3UOB