Cellular response to efficient dUTPase RNAi silencing in stable HeLa cell lines perturbs expression levels of genes involved in thymidylate metabolism.

Merényi, Gábor and Kovári, Júlia and Tóth, Judit and Takács, Enikő and Zagyva, Imre and Erdei, Anna and Vértessy G., Beáta (2011) Cellular response to efficient dUTPase RNAi silencing in stable HeLa cell lines perturbs expression levels of genes involved in thymidylate metabolism. NUCLEIC ACIDS RESEARCH, 30 (6). pp. 369-390. ISSN 0305-1048

Preview

Text 6. Cellular response to efficient dUTPase Merényi.pdf Download (810kB) | Preview

Abstract

dUTPase is involved in preserving DNA integrity in cells. We report an efficient dUTPase silencing by RNAi-based system in stable human cell line. Repression of dUTPase induced specific expression level increments for thymidylate kinase and thymidine kinase, and also an increased sensitization to 5-fluoro-2'-deoxyuridine and 5-fluoro-uracil. The catalytic mechanism of dUTPase was investigated for 5-fluoro-dUTP. The 5F-substitution on the uracil ring of the substrate did not change the kinetic mechanism of dUTP hydrolysis by dUTPase. Results indicate that RNAi silencing of dUTPase induces a complex cellular response wherein sensitivity towards fluoropyrimidines and gene expression levels of related enzymes are both modulated.

Actions (login required)

Edit Item