Cellular Response to Efficient dUTPase RNAi Silencing in Stable HeLa Cell Lines Perturbs Expression Levels of Genes Involved in Thymidylate Metabolism

REFERENCES

• Vertessy , B. G. and Toth , J. 2009 . Keeping uracil out of DNA: physiological role, structure and catalytic mechanism of dUTPases . Acc. Chem. Res. , 42 : 97 – 106 .
   PubMed Web of Science ®Google Scholar
• Ladner , R. D. 2001 . The role of dUTPase and uracil-DNA repair in cancer chemotherapy . Curr Protein Pept Sci , 2 : 361 – 370 .
   PubMed Web of Science ®Google Scholar
• el-Hajj , H. H. , Zhang , H. and Weiss , B. 1988 . Lethality of a dut (deoxyuridine triphosphatase) mutation in Escherichia coli . J. Bacteriol. , 170 : 1069 – 1075 .
   PubMed Web of Science ®Google Scholar
• Gadsden , M. H. , McIntosh , E. M. , Game , J. C. , Wilson , P. J. and Haynes , R. H. 1993 . dUtp pyrophosphatase is an essential enzyme in Saccharomyces cerevisiae . Embo. J. , 12 : 4425 – 4431 .
   PubMed Web of Science ®Google Scholar
• Koehler , S. E. and Ladner , R. D. 2004 . Small interfering RNA-mediated suppression of dUTPase sensitizes cancer cell lines to thymidylate synthase inhibition . Mol. Pharmacol. , 66 : 620 – 626 .
   PubMed Web of Science ®Google Scholar
• Ahmad , S. I. , Kirk , S. H. and Eisenstark , A. 1998 . Thymine metabolism and thymineless death in prokaryotes and eukaryotes . Annu. Rev. Microbiol. , 52 : 591 – 625 .
   PubMed Web of Science ®Google Scholar
• Goulian , M. , Bleile , B. M. , Dickey , L. M. , Grafstrom , R. H. , Ingraham , H. A. , Neynaber , S. A. , Peterson , M. S. and Tseng , B. Y. 1986 . Mechanism of thymineless death . Adv. Exp. Med. Biol. B , 195 : 89 – 95 .
   PubMedGoogle Scholar
• Longley , D. B. , Harkin , D. P. and Johnston , P. G. 2003 . 5-fluorouracil: mechanisms of action and clinical strategies . Nat. Rev. Cancer , 3 : 330 – 338 .
   PubMed Web of Science ®Google Scholar
• Noordhuis , P. , Holwerda , U. , Van der Wilt , C. L. , Van Groeningen , C. J. , Smid , K. , Meijer , S. , Pinedo , H. M. and Peters , G. J. 2004 . 5-Fluorouracil incorporation into RNA and DNA in relation to thymidylate synthase inhibition of human colorectal cancers . Ann. Oncol. , 15 : 1025 – 1032 .
   PubMed Web of Science ®Google Scholar
• Kufe , D. W. and Major , P. P. 1981 . 5-Fluorouracil incorporation into human breast carcinoma RNA correlates with cytotoxicity . J. Biol. Chem. , 256 : 9802 – 9805 .
   PubMed Web of Science ®Google Scholar
• Ingraham , H. A. , Tseng , B. Y. and Goulian , M. 1982 . Nucleotide levels and incorporation of 5-fluorouracil and uracil into DNA of cells treated with 5-fluorodeoxyuridine . Mol. Pharmacol. , 21 : 211 – 216 .
   PubMed Web of Science ®Google Scholar
• Ghoshal , K. and Jacob , S. T. 1994 . Specific inhibition of pre-ribosomal RNA processing in extracts from the lymphosarcoma cells treated with 5-fluorouracil . Cancer Res. , 54 : 632 – 636 .
   PubMed Web of Science ®Google Scholar
• Showalter , S. L. , Showalter , T. N. , Witkiewicz , A. , Havens , R. , Kennedy , E. P. , Hucl , T. , Kern , S. E. , Yeo , C. J. and Brody , J. R. 2008 . Evaluating the drug-target relationship between thymidylate synthase expression and tumor response to 5-fluorouracil. Is it time to move forward? . Cancer Biol. Ther. , 7 : 986 – 994 .
   PubMed Web of Science ®Google Scholar
• Kanamaru , R. , Kakuta , H. , Sato , T. , Ishioka , C. and Wakui , A. 1986 . The inhibitory effects of 5-fluorouracil on the metabolism of preribosomal and ribosomal RNA in L-1210 cells in vitro . Cancer Chemother. Pharmacol. , 17 : 43 – 46 .
   PubMed Web of Science ®Google Scholar
• Doong , S. L. and Dolnick , B. J. 1998 . 5-Fluorouracil substitution alters pre-mRNA splicing in vitro . J. Biol. Chem. , 263 : 4467 – 4473 .
   Google Scholar
• Canman , C. E. , Radany , E. H. , Parsels , L. A. , Davis , M. A. , Lawrence , T. S. and Maybaum , J. 2004 . Induction of resistance to fluorodeoxyuridine cytotoxicity and DNA damage in human tumor cells by expression of Escherichia coli deoxyuridinetriphosphatase . Cancer Res. , 54 : 2296 – 2298 .
   Google Scholar
• Webley , S. D. , Hardcastle , A. , Ladner , R. D. , Jackman , A. L. and Aherne , G. W. 2000 . Deoxyuridine triphosphatase (dUTPase) expression and sensitivity to the thymidylate synthase (TS) inhibitor ZD9331 . Br. J. Cancer , 83 : 792 – 799 .
   PubMed Web of Science ®Google Scholar
• Studebaker , A. W. , Lafuse , W. P. , Kloesel , R. and Williams , M. V. 2005 . Modulation of human dUTPase using small interfering RNA . Biochem. Biophys. Res. Commun. , 327 : 306 – 310 .
   PubMed Web of Science ®Google Scholar
• Kajimoto , S. , Horie , M. , Manabe , H. , Masuda , Y. , Shibayama-Imazu , T. , Nakajo , S. , Gong , X. F. , Obama , T. , Itabe , H. and Nakaya , K. 2008 . A tyrosine kinase inhibitor, beta-hydroxyisovalerylshikonin, induced apoptosis in human lung cancer DMS114 cells through reduction of dUTP nucleotidohydrolase activity . Biochim. Biophys. Acta , 1782 : 41 – 50 .
   PubMed Web of Science ®Google Scholar
• Hu , C. M. and Chang , Z. F. 2008 . Synthetic lethality by lentiviral short hairpin RNA silencing of thymidylate kinase and doxorubicin in colon cancer cells regardless of the p53 status . Cancer Res. , 68 : 2831 – 2840 .
   PubMed Web of Science ®Google Scholar
• Chu , E. , Voeller , D. M. , Jones , K. L. , Takechi , T. , Maley , G. F. , Maley , F. , Segal , S. and Allegra , C. J. 1994 . Identification of a thymidylate synthase ribonucleoprotein complex in human colon cancer cells . Mol. Cell Biol. , 14 : 207 – 213 .
   PubMed Web of Science ®Google Scholar
• Ladner , R. D. , Lynch , F. J. , Groshen , S. , Xiong , Y. P. , Sherrod , A. , Caradonna , S. J. , Stoehlmacher , J. and Lenz , H. J. 2000 . dUTP nucleotidohydrolase isoform expression in normal and neoplastic tissues: association with survival and response to 5-fluorouracil in colorectal cancer . Cancer Res , 60 : 3493 – 3503 .
   PubMed Web of Science ®Google Scholar
• Parsels , L. A. , Parsels , J. D. , Wagner , L. M. , Loney , T. L. , Radany , E. H. and Maybaum , J. 1998 . Mechanism and pharmacological specificity of dUTPase-mediated protection from DNA damage and cytotoxicity in human tumor cells . Cancer Chemother. Pharmacol. , 42 : 357 – 362 .
   PubMed Web of Science ®Google Scholar
• An , Q. , Robins , P. , Lindahl , T. and Barnes , D. E. 2007 . 5-Fluorouracil incorporated into DNA is excised by the Smug1 DNA glycosylase to reduce drug cytotoxicity . Cancer Res. , 67 : 940 – 945 .
   PubMed Web of Science ®Google Scholar
• Sclafani , R. A. and Fangman , W. L. 1984 . Yeast gene CDC8 encodes thymidylate kinase and is complemented by herpes thymidine kinase gene TK . Proc. Natl. Acad. Sci. USA , 81 : 5821 – 5825 .
   PubMed Web of Science ®Google Scholar
• Caradonna , S. J. and Cheng , Y. C. 1980 . The role of deoxyuridine triphosphate nucleotidohydrolase, uracil-DNA glycosylase, and DNA polymerase alpha in the metabolism of FUdR in human tumor cells . Mol. Pharmacol. , 18 : 513 – 520 .
   PubMed Web of Science ®Google Scholar
• Quesada-Soriano , I. , Casas-Solvas , J. M. , Recio , E. , Ruiz-Perez , L. M. , Vargas-Berenguel , A. , Gonzalez-Pacanowska , D. and Garcia-Fuentes , L. 2010 . Kinetic properties and specificity of trimeric Plasmodium falciparum and human dUTPases . Biochimie , 92 : 178 – 186 .
   PubMed Web of Science ®Google Scholar
• Toth , J. , Varga , B. , Kovacs , M. , Malnasi-Csizmadia , A. and Vertessy , B. G. 2007 . Kinetic mechanism of human dUTPase, an essential nucleotide pyrophosphatase enzyme . J. Biol. Chem. , 282 : 33572 – 33582 .
   PubMed Web of Science ®Google Scholar
• Vertessy , B. G. 1997 . Flexible glycine rich motif of Escherichia coli deoxyuridine triphosphate nucleotidohydrolase is important for functional but not for structural integrity of the enzyme . Proteins , 28 : 568 – 579 .
   PubMed Web of Science ®Google Scholar
• Santi , D. V. , McHenry , C. S. and Sommer , H. 1974 . Mechanism of interaction of thymidylate synthetase with 5-fluorodeoxyuridylate . Biochemistry , 13 : 471 – 481 .
   PubMed Web of Science ®Google Scholar
• Lavie , A. and Konrad , M. 2004 . Structural requirements for efficient phosphorylation of nucleotide analogs by human thymidylate kinase . Mini Rev. Med. Chem. , 4 : 351 – 359 .
   PubMed Web of Science ®Google Scholar
• Pfaffl , M. W. 2001 . A new mathematical model for relative quantification in real-time RT-PCR . Nucleic Acids Res. , 29 : e45
   PubMed Web of Science ®Google Scholar
• Barabas , O. , Rumlova , M. , Erdei , A. , Pongracz , V. , Pichova , I. and Vertessy , B. G. 2003 . dUTPase and nucleocapsid polypeptides of the Mason-Pfizer monkey virus form a fusion protein in the virion with homotrimeric organization and low catalytic efficiency . J. Biol. Chem. , 278 : 38803 – 38812 .
   PubMed Web of Science ®Google Scholar
• Varga , B. , Barabas , O. , Kovari , J. , Toth , J. , Hunyadi-Gulyas , E. , Klement , E. , Medzihradszky , K. F. , Tolgyesi , F. , Fidy , J. and Vertessy , B. G. 2007 . Active site closure facilitates juxtaposition of reactant atoms for initiation of catalysis by human dUTPase . FEBS Lett. , 581 : 4783 – 4788 .
   PubMed Web of Science ®Google Scholar
• Bekesi , A. , Zagyva , I. , Hunyadi-Gulyas , E. , Pongracz , V. , Kovari , J. , Nagy , A. O. , Erdei , A. , Medzihradszky , K. F. and Vertessy , B. G. 2004 . Developmental regulation of dUTPase in drosophila melanogaster . J. Biol. Chem. , 279 : 22362 – 22370 .
   PubMed Web of Science ®Google Scholar
• Chan , K. M. , Delfert , D. and Junger , K. D. 1986 . A direct colorimetric assay for Ca2+-stimulated ATPase activity . Anal. Biochem. , 157 : 375 – 380 .
   PubMed Web of Science ®Google Scholar
• Varga , B. , Barabas , O. , Takacs , E. , Nagy , N. , Nagy , P. and Vertessy , B. G. 2008 . Active site of mycobacterial dUTPase: structural characteristics and a built-in sensor . Biochem. Biophys. Res. Commun. , 373 : 8 – 13 .
   PubMed Web of Science ®Google Scholar
• Mustafi , D. , Bekesi , A. , Vertessy , B. G. and Makinen , M. W. 2003 . Catalytic and structural role of the metal ion in dUTP pyrophosphatase . Proc. Natl. Acad. Sci. USA , 100 : 5670 – 5675 .
   PubMed Web of Science ®Google Scholar
• Kovari , J. , Barabas , O. , Varga , B. , Bekesi , A. , Tolgyesi , F. , Fidy , J. , Nagy , J. and Vertessy , B. G. 2008 . Methylene substitution at the alpha-beta bridging position within the phosphate chain of dUDP profoundly perturbs ligand accommodation into the dUTPase active site . Proteins , 71 : 308 – 319 .
   PubMed Web of Science ®Google Scholar