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

Gabor Merényi, Julia Kovári, Judit Tóth, Enikõ Takács, Imre Zagyva, Anna Erdei, Beata G. Vértessy

Research output: Contribution to journalArticle

17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)369-390
Number of pages22
JournalNucleosides, Nucleotides and Nucleic Acids
Volume30
Issue number6
DOIs
Publication statusPublished - Jun 1 2011

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Keywords

  • 5-fluoro-2'-deoxyuridine
  • 5-fluoro-uracil
  • RNAi
  • dUTPase
  • thymidylate metabolism

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Genetics

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