Depletion of uracil-DNA glycosylase activity is associated with decreased cell proliferation

Biochem Biophys Res Commun. 2005 Aug 26;334(2):509-15. doi: 10.1016/j.bbrc.2005.06.118.


Uracil-DNA glycosylase (UNG) is the primary enzyme responsible for removing uracil residues from DNA. Increasing evidence suggests that UNG may be a potential target for the development of novel antiviral and/or anticancer agents. To determine whether the uracil-DNA glycosylase inhibitor protein (UGI) could be used to specifically target UNGs intracellularly, we developed a construct that expresses UGI as a fusion protein with the TAT-protein transduction domain and described a novel method for the purification of recombinant TAT-UGI. Treatment of several cell types with TAT-UGI resulted in a dose- and time-dependent decrease in UNG activity. A somewhat surprising effect of TAT-UGI treatment was the decrease in cell proliferation, but not in cell viability. The results of this study support the premise that UNG can be used as a potential therapeutic target and also demonstrate that protein transduction can be used to modulate UNG activity.

MeSH terms

  • Apoptosis*
  • Cell Proliferation
  • DNA Glycosylases / deficiency*
  • DNA Glycosylases / genetics
  • Enzyme Activation
  • Gene Transfer Techniques
  • HT29 Cells
  • HeLa Cells
  • Humans
  • Uracil-DNA Glycosidase
  • Viral Proteins / genetics
  • Viral Proteins / metabolism*


  • Viral Proteins
  • uracil-DNA glycosylase inhibitor protein, B. subtilis bacteriophage
  • DNA Glycosylases
  • Uracil-DNA Glycosidase