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  • Title: Depletion of uracil-DNA glycosylase activity is associated with decreased cell proliferation.
    Author: Studebaker AW, Ariza ME, Williams MV.
    Journal: Biochem Biophys Res Commun; 2005 Aug 26; 334(2):509-15. PubMed ID: 16005850.
    Abstract:
    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.
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