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

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.

authors

Studebaker AW,Ariza ME,Williams MV

doi

10.1016/j.bbrc.2005.06.118

subject

Has Abstract

pub_date

2005-08-26 00:00:00

pages

509-15

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(05)01375-6

journal_volume

334

pub_type

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