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Clustered base substitutions in CTP synthetase conferring drug resistance in Chinese hamster ovary cells

Nature Genetics volume 3, pages 317–322 (1993)Cite this article

Abstract

Dominantly acting mutations that eliminate the allosteric regulation of CTP synthetase confer a form of multidrug resistance and a mutator phenotype to cultured Chinese hamster ovary cells. Mutations responsible for this phenotype have been identified in 23 independent strains selected for resistance to arabinosyl cytosine and 5-fluorouracil. All these mutations were due to base substitutions at seven sites within a highly conserved region of the ctps gene. This clustering should make it feasible to assess the role of such mutations in the development of drug resistance encountered in the treatment of malignant disease.

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Author notes

  1. Geraldine Phear & Mark Meuth

    Present address: Section of Experimental Oncology, Eccles Institute of Human Genetics, Building 533, University of Utah, Salt Lake City, Utah, 84112, USA

  2. Masatake Yamauchi

    Present address: National Institute of Radiological Sciences, 4-9-1 Anagawa, Chiba, 260, Japan

Authors and Affiliations

  1. Imperial Cancer Research Fund, Clare Hall Laboratories, Blanche Lane, South Mimms, Hertfordshire, EN6 3LD, UK

    Jeremy Whelan, Geraldine Phear, Masatake Yamauchi & Mark Meuth

  2. Imperial Cancer Research Fund, Department of Medical Oncology, St. Bartholomew's Hospital, London, EC1A 7BE, UK

    Jeremy Whelan

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  3. Masatake Yamauchi
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  4. Mark Meuth
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Whelan, J., Phear, G., Yamauchi, M. et al. Clustered base substitutions in CTP synthetase conferring drug resistance in Chinese hamster ovary cells. Nat Genet 3, 317–322 (1993). https://doi.org/10.1038/ng0493-317

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