Modulation of human dUTPase using small interfering RNA.
Biochem Biophys Res Commun
; 327(1): 306-10, 2005 Feb 04.
Article
in En
| MEDLINE
| ID: mdl-15629463
ABSTRACT
Deoxyuridine triphosphate nucleotidohydrolase (dUTPase) is responsible for maintaining low intracellular levels of dUTP, thus preventing the incorporation of dUTP into DNA. A 21 bp double-stranded RNA molecule (siRNAdUT3) targeted against motif 3 of human dUTPase resulted in a time- and dose-dependent decrease in dUTPase activity in transfected cells. dUTPase activity was reduced approximately 95+/-5% in all cell lines tested 48 h after transfection with 2 microg siRNAdUT3 and it was maintained at this decreased level for at least 72 h. Down-regulation of dUTPase resulted in a significant increase in intracellular dUTP and a decreased proliferation of the transfected cells. Therefore, we conclude that dUTPase activity/expression can be down-regulated using siRNA specifically targeted to dUTPase mRNA and that this approach can be used to elucidate the role of dUTPase in DNA metabolism, as well as, to determine whether dUTPase is a valid target for drug development.
Search on Google
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyrophosphatases
/
Gene Expression Regulation
/
RNA, Small Interfering
Limits:
Humans
Language:
En
Journal:
Biochem Biophys Res Commun
Year:
2005
Document type:
Article
Affiliation country:
United States