Mammalian mutants genetically altered in CTP synthetase activity

A clone (FURT-1A) was isolated by virtue of its resistance to 1uM 5fluorouracil from wildtype mouse lymphoma cells. In comparative growth rate experiments, FURT-1A cells were also less sensitive than parental cells to the growth of inhibitory effects of thymidine, deoxyguanosine, 5-fluouridine, and arabinosylcytosine. Metabolic flux experiments with tritium-uridine in situ indicate that FURT-1A cells had a 2-fold enhanced rate of conversion of UTP to CTP. Kinetic analyses indicated that the CTP synthetase activity in extracts of FURT-1A cells was refractory to inhibition by CTP. The genetic loss of normal allosteric inhibition of the CTP synthetase activity in FURT-1A cells could account for the nusual phenotypic properties of these cells