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Pleiotropic mutants of Chinese hamster cells with altered cytidine 5′-triphosphate synthetase (1984)

Abstract
Following chemical mutagenesis and multiple-step indirect selection, four clones of Chinese hamster V79 cells were isolated which exhibited auxotrophy for thymidine, deoxycytidine, or deoxyuridine but not for cytidine or uridine. All were resistant to uridine, 3-deazauridine, 5-fluorouridine, thymidine, and cytosine arabinoside at concentrations that were toxic to wild-type V79 cells. The cytidine 5′-triphosphate (CTP) and deoxycytidine 5′-triphosphate (dCTP) pools in the mutants were expanded, but the uridine 5′-triphosphate (UTP) pool either decreased or remained unchanged relative to the wild-type level. Furthermore, since the parental cells appear to be deficient in dCMP deaminase activity and CTP (or one of its metabolites) has been shown to inhibit uridine 5′-diphosphate (UDP) reduction, an elevated CTP level should lead to the observed thymidine auxotrophy. It also explains the joint resistance of mutant clones to thymidine and cytosine arabinoside. The change in the ratio of intracellular dCTP to thymidine 5′-triphosphate (dTTP) may be responsible for the elevation in the rates of spontaneous mutations in these mutants.. Peer Reviewed. http://deepblue.lib.umich.edu/bitstream/2027.42/44150/1/10528_2004_Article_BF00485854.pdf

Publication details
Download , http://hdl.handle.net/2027.42/44150
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=6497832&dopt=citation
Publisher Kluwer Academic Publishers-Plenum Publishers; Plenum Publishing Corporation ; Springer Science+Business Media
Contributors Lawrence D. Buhl Center for Human Genetics, Department of Human Genetics, University of Michigan Medical School, 48109, Ann Arbor, Michigan, Lawrence D. Buhl Center for Human Genetics, Department of Human Genetics, University of Michigan Medical School, 48109, Ann Arbor, Michigan, Lawrence D. Buhl Center for Human Genetics, Department of Human Genetics, University of Michigan Medical School, 48109, Ann Arbor, Michigan, Lawrence D. Buhl Center for Human Genetics, Department of Human Genetics, University of Michigan Medical School, 48109, Ann Arbor, Michigan, Ann Arbor
Repository University of Michigan (United States)
Keywords Human Genetics, cytidine 5′-triphosphate synthetase, nucleotide pools, Biomedicine, Medical Microbiology, Biochemistry, general, Zoology, Chinese hamster cells, pyrimidine metabolism, K m mutants, feedback inhibition, Molecular, Cellular and Developmental Biology, Natural Resources and Environment, Ecology and Evolutionary Biology, Science, Health Sciences
Language English

Publications citing this publication (1)
The kinetics and feedback inhibition of cytidine 5′-triphosphate synthetase in wild-type and mutant Chinese hamster cells (1984)

Cited publications (6)
Estimation of mutation rates in cultured mammalian cells (1983)
Characterization of a mutator gene in Chinese hamster ovary cells.
Multienzyme complex for metabolic channeling in mammalian DNA replication.
Thymineless Mutagenesis in Bacteriophage T4
Isolation of Chinese hamster cell mutants deficient in dihydrofolate reductase activity.
Mutagenesis during in vitro DNA synthesis; a dissertation in physiology. (1977)