Isolation and characterization of 5-fluorouracil-resistant mutants of Chinese hamster ovary cells deficient in the activities of orotate phosphoribosyltransferase and orotidine 5'-monophosphate decarboxylase. 1980

D Patterson

A rapid, simple method for isolation of large numbers of Chinese hamster ovary cell (CHO-K1) mutants deficient in the final two enzymes of UMP biosynthesis, orotate phosphoribosyltransferase (EC 2.4.2.10), and OMP decarboxylase (EC 4.1.1.23) is described. The method takes advantage of the fact that CHO-K1 cells require orotate phosphoribosyltransferase to activate the pyrimidine analog 5-fluorouracil to its active form; hence, mutants lacking thhe relevance of these observations to the metabolism of this cancer chemotheraputic agent, to the study of the structure of the protein(s) involved in catalyzing the last two steps of UMP biosynthesis, to the study of the structure of the gene(s) coding for this protein, and to analysis of the human genetic disease orotic aciduria is discussed.

UI MeSH Term Description Entries
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D009962 Orotate Phosphoribosyltransferase The enzyme catalyzing the formation of orotidine-5'-phosphoric acid (orotidylic acid) from orotic acid and 5-phosphoribosyl-1-pyrophosphate in the course of pyrimidine nucleotide biosynthesis. EC 2.4.2.10. Orotidine-5'-Phosphate Pyrophosphorylase,Orotidylic Acid Phosphorylase,OMPase,Orotidine-5'-Monophosphate Phosphohydrolase,Orotidine 5' Monophosphate Phosphohydrolase,Orotidine 5' Phosphate Pyrophosphorylase,Phosphohydrolase, Orotidine-5'-Monophosphate,Phosphoribosyltransferase, Orotate,Phosphorylase, Orotidylic Acid,Pyrophosphorylase, Orotidine-5'-Phosphate
D009964 Orotidine-5'-Phosphate Decarboxylase Orotidine-5'-phosphate carboxy-lyase. Catalyzes the decarboxylation of orotidylic acid to yield uridylic acid in the final step of the pyrimidine nucleotide biosynthesis pathway. EC 4.1.1.23. Orotidine Phosphate Carboxy-Lyase,Orotidylate Decarboxylase,OMP Decarboxylase,Orotidine 5 Phosphate Decarboxylase,Orotidine 5' Phosphate Decarboxylase,Orotidine-5-Phosphate Decarboxylase,Carboxy-Lyase, Orotidine Phosphate,Decarboxylase, OMP,Decarboxylase, Orotidine-5'-Phosphate,Decarboxylase, Orotidine-5-Phosphate,Decarboxylase, Orotidylate,Orotidine Phosphate Carboxy Lyase,Phosphate Carboxy-Lyase, Orotidine
D010053 Ovary The reproductive organ (GONADS) in female animals. In vertebrates, the ovary contains two functional parts: the OVARIAN FOLLICLE for the production of female germ cells (OOGENESIS); and the endocrine cells (GRANULOSA CELLS; THECA CELLS; and LUTEAL CELLS) for the production of ESTROGENS and PROGESTERONE. Ovaries
D010430 Pentosyltransferases Enzymes of the transferase class that catalyze the transfer of a pentose group from one compound to another.
D002262 Carboxy-Lyases Enzymes that catalyze the addition of a carboxyl group to a compound (carboxylases) or the removal of a carboxyl group from a compound (decarboxylases). EC 4.1.1. Carboxy-Lyase,Decarboxylase,Decarboxylases,Carboxy Lyase,Carboxy Lyases
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002999 Clone Cells A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed) Clones,Cell, Clone,Cells, Clone,Clone,Clone Cell
D004351 Drug Resistance Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. Resistance, Drug
D005260 Female Females

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D Patterson
January 1981, Transactions of the Royal Society of Tropical Medicine and Hygiene,
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