tRNA Modifying Enzymes, NSUN2 and METTL1, Determine Sensitivity to 5-Fluorouracil in HeLa Cells

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tRNA Modifying Enzymes, NSUN2 and METTL1, Determine Sensitivity to 5-Fluorouracil in HeLa Cells

Nonessential tRNA modifications by methyltransferases are evolutionarily conserved and have been reported to stabilize mature tRNA molecules and prevent rapid tRNA decay (RTD). The tRNA modifying enzymes, NSUN2 and METTL1, are mammalian orthologs of yeast Trm4 and Trm8, which are required for protecting tRNA against RTD. A simultaneous overexpression of NSUN2 and METTL1 is widely observed among...

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Evidence that tRNA modifying enzymes are important in vivo targets for 5-fluorouracil in yeast.

We have screened a collection of haploid yeast knockout strains for increased sensitivity to 5-fluorouracil (5-FU). A total of 138 5-FU sensitive strains were found. Mutants affecting rRNA and tRNA maturation were particularly sensitive to 5-FU, with the tRNA methylation mutant trm10 being the most sensitive mutant. This is intriguing since trm10, like many other tRNA modification mutants, lack...

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Six cell lines differing in histological origin were studied regarding the growth inhibitory effect of fluoropyrimidines in relation to their metabolism. The human colon carcinoma cell line WiDr was most sensitive to 5-fluorouracil (FUra) (50% growth inhibitory concentration, 0.7 microM) and to its analogue 5'deoxy-5-fluorouridine (5'dFUR) (50% growth inhibitory concentration, 18 microM). The m...

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Cytotoxic and Cytokinetic Effects of Thymidine, 5-Fluorouracil, and Deoxycytidine on HeLa Cells in Culture1

Exponentially growing HeLa cells were exposed to thymidine (dThd), 5-fluorouracil (FUra), and deoxycytidine (dCyd) singly and in combination for up to 3 days. Survivals were measured using a colony forming assay, and cytokinetic effects of the drugs were evaluated by flow cytometry and by determination of population growth rates. Increasing concentrations of dThd alone (up to 4 HIM) progressive...

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Cytotoxic and cytokinetic effects of thymidine, 5-fluorouracil, and deoxycytidine on HeLa cells in culture.

Exponentially growing HeLa cells were exposed to thymidine (dThd), 5-fluorouracil (FUra), and deoxycytidine (dCyd) singly and in combination for up to 3 days. Survivals were measured using a colony forming assay, and cytokinetic effects of the drugs were evaluated by flow cytometry and by determination of population growth rates. Increasing concentrations of dThd alone (up to 4 mM) progressivel...

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ژورنال

عنوان ژورنال: PLoS Genetics

سال: 2014

ISSN: 1553-7404

DOI: 10.1371/journal.pgen.1004639