1887

Abstract

Phosphoribosyl-pyrophosphate synthetase (Prs) catalyses the synthesis of phosphoribosyl pyrophosphate (PRPP), an intermediate in nucleotide metabolism and the biosynthesis of the amino acids histidine and tryptophan. The genome contains a family of five genes, . Using anti-peptide antisera directed against two different epitopes of Prs1p it was shown that Prs1p localizes to granular cytoplasmic structures. This localization was confirmed by living cell microscopy of strains expressing a functional green fluorescent protein (GFP)-tagged Prs1p. Analysis of Prs1p distribution in conditional secretory-deficient () mutants suggested that the observed distribution of Prs1p is independent of the secretory pathway. Electron microscopy revealed that plasma membrane invaginations and accumulation of cytoplasmic vesicles were more frequent in strains which lack some of the genes than in the wild-type. The fact that Δ and Δ are hypersensitive to caffeine and unable to recover from exposure to it as judged by the release of alkaline phosphatase points to a possible link between Prs and the maintenance of cell integrity.

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2000-12-01
2019-10-22
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References

  1. Becker, M. A., Puig, J. G., Mateos, F. A., Jimenez, M., Kim, M. & Simonds, H. A. ( 1988; ). Inherited superactivity of phosphoribosylpyrophosphate synthetase: association of uric acid overproduction and sensorineural deafness. Am J Med 85, 383-390.[CrossRef]
    [Google Scholar]
  2. Becker, M. A., Smith, P. R., Taylor, W., Mustafi, R. & Switzer, R. L. ( 1995; ). The genetic and functional basis of purine nucleotide feedback-resistant phosphoribosylpyrophosphate synthetase superactivity. J Clin Invest 96, 2133-2141.[CrossRef]
    [Google Scholar]
  3. Binley, K. M., Radcliffe, P. A., Trevethick, J., Duffy, K. A. & Sudbery, P. E. ( 1999; ). The yeast PRS3 gene is required for cell integrity, cell cycle arrest upon nutrient deprivation, ion homeostasis and the proper organization of the actin cytoskeleton. Yeast 15, 1459-1469.[CrossRef]
    [Google Scholar]
  4. Boeke, J., Trueheart, J., Natsoulis, G. & Fink, G. R. ( 1987; ). 5-Fluoro-orotic acid as a selective agent in yeast molecular genetics. Methods Enzymol 154, 164-175.
    [Google Scholar]
  5. Carter, A. T., Narbad, A., Pearson, B. M., Beck, K.-F., Logghe, M., Contreras, R. & Schweizer, M. ( 1994; ). Phosphoribosylpyrophosphate synthetase (PRS): a new gene family in Saccharomyces cerevisiae. Yeast 10, 1031-1044.[CrossRef]
    [Google Scholar]
  6. Carter, A. T., Beiche, F., Hove-Jensen, B., Narbad, A., Barker, P. J., Schweizer, L. M. & Schweizer, M. ( 1997; ). PRS1 is a key member of the gene family encoding phosphoribosylpyrophosphate synthetase in Saccharomyces cerevisiae. Mol Gen Genet 254, 148-156.[CrossRef]
    [Google Scholar]
  7. Cid, V. J., Durán, A., del Rey, F., Snyder, M. P., Nombela, C. & Sánchez, M. ( 1995; ). Molecular basis of cell integrity and morphogenesis in Saccharomyces cerevisiae. Microbiol Rev 59, 345-386.
    [Google Scholar]
  8. Daum, G., Böhni, P. C. & Schatz, G. ( 1982; ). Import of proteins into mitochondria. Cytochrome b 2 and cytrochrome c peroxidase are located in the intermembrane space of yeast mitochondria. J Biol Chem 257, 13028-13033.
    [Google Scholar]
  9. Gaigg, G., Simbeni, R., Hrastnik, C., Paltauf, F. & Daum, G. ( 1995; ). Characterization of a microsomal subfraction associated with mitochondria of the yeast, Saccharomyces cerevisiae. Biochim Biophys Acta 1234, 214-220.[CrossRef]
    [Google Scholar]
  10. Gietz, R. D. & Woods, R. A. ( 1994; ). High efficiency transformation with lithium acetate. In Molecular Genetics of Yeast. A Practical Approach , pp. 121-131. Edited by J. R. Johnson. Oxford:IRL Press.
  11. Güldener, U., Heck, S., Fiedler, T., Beinhauer, J. & Hegemann, J. H. ( 1996; ). A new efficient gene disruption cassette for repeated use in budding yeast. Nucleic Acids Res 24, 2519-2524.[CrossRef]
    [Google Scholar]
  12. Hampsey, M. ( 1997; ). A review of phenotypes in Saccharomyces cerevisiae. Yeast 13, 1099-1133.[CrossRef]
    [Google Scholar]
  13. Heim, R. & Tsien, R. Y. ( 1996; ). Engineering green fluorescent protein for improved brightness, longer wavelengths and fluorescence resonance energy transfer. Curr Biol 6, 178-182.[CrossRef]
    [Google Scholar]
  14. Hernando, Y., Parr, A. & Schweizer, M. ( 1998; ). PRS5, the fifth member of the phosphoribosyl pyrophosphate synthetase gene family in Saccharomyces cerevisiae, is essential for viability in the absence of either PRS1 or PRS3. J Bacteriol 180, 6404-6407.
    [Google Scholar]
  15. Hernando, Y., Carter, A. T., Parr, A., Hove-Jensen, B. & Schweizer, M. ( 1999; ). Genetic analysis and enzyme activity suggest the existence of more than one minimal functional unit capable of synthesising phosphoribosyl pyrophosphate in Saccharomyces cerevisiae. J Biol Chem 274, 12480-12487.[CrossRef]
    [Google Scholar]
  16. Hove-Jensen, B. ( 1989; ). Phosphoribosylpyrophosphate (PRPP)-less mutants of Escherichia coli. Mol Microbiol 3, 1487-1492.[CrossRef]
    [Google Scholar]
  17. Hurt, E. C., McDowall, A. & Schimmang, T. ( 1988; ). Nucleolar and nuclear envelope proteins of the yeast Saccharomyces cerevisiae. Eur J Cell Biol 46, 554-563.
    [Google Scholar]
  18. Kadowaki, T., Schneiter, R., Hitomi, M. & Tartakoff, A. M. ( 1995; ). Mutations in nucleolar proteins lead to nucleolar accumulation of poly(A)+ RNA in Saccharomyces cerevisiae. Mol Cell Biol 6, 1103-1110.[CrossRef]
    [Google Scholar]
  19. Kaiser, C., Michaelis, S. & Mitchell, A. (1994). Methods in Yeast Genetics. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.
  20. Khorana, H. G., Fernandes, J. F. & Kornberg, A. ( 1958; ). Pyrophosphorylation of ribose-5-phosphate in the enzymatic synthesis of 5-phosphorylribose 1-pyrophosphate. J Biol Chem 230, 941-948.
    [Google Scholar]
  21. Leber, A., Hrastnik, C. & Daum, G. ( 1995; ). Phospholipid-synthesizing enzymes in Golgi membranes of the yeast Saccharomyces cerevisiae. FEBS Lett 377, 271-274.[CrossRef]
    [Google Scholar]
  22. Novick, P., Field, C. & Schekman, R. ( 1980; ). Identification of 23 complementation groups required for post-translational events in the yeast secretory pathway. Cell 21, 205-215.[CrossRef]
    [Google Scholar]
  23. Pearson, B. M., Hernando, Y. & Schweizer, M. ( 1998; ). Construction of PCR-ligated long flanking homology cassettes for use in the functional analysis of six unknown open reading frames from the left and right arms of Saccharomyces cerevisiae chromosome XV. Yeast 14, 391-399.[CrossRef]
    [Google Scholar]
  24. Posas, F., Casamayor, A. & Ariño, J. ( 1993; ). The PPZ protein phosphatases are involved in the maintenance of osmotic stability of yeast cells. FEBS Lett 318, 282-286.[CrossRef]
    [Google Scholar]
  25. Rapoport, T. A., Jungnickel, B. & Kutay, U. ( 1996; ). Protein transport across the eucaryotic endoplasmic reticulum and bacterial inner membranes. Annu Rev Biochem 65, 271-303.[CrossRef]
    [Google Scholar]
  26. Sakakibara, Y. ( 1992; ). dnaR function of the prs gene of Escherichia coli in initiation of chromosome replication. J Mol Biol 226, 989-996.[CrossRef]
    [Google Scholar]
  27. Sambrook, J., Fritsch, E. F. & Maniatis, T. (1989). Molecular Cloning: a Laboratory Manual, 2nd edn. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory.
  28. Schekman, R. ( 1985; ). Protein localization and membrane traffic in yeast. Annu Rev Cell Biol 1, 115-143.[CrossRef]
    [Google Scholar]
  29. Serrano, R. ( 1988; ). H+-ATPase from plasma membranes of Saccharomyces cerevisiae and Avena sativa roots: purification and reconstitution. Methods Enzymol 157, 533-544.
    [Google Scholar]
  30. Sikorski, R. S. & Hieter, P. ( 1989; ). A system of shuttle vectors and yeast host strains designed for efficient manipulation in Saccharomyces cerevisiae. Genetics 122, 19-27.
    [Google Scholar]
  31. Stark, M. J. R. ( 1999; ). Protein phoshorylation and dephosphorylation. In The Metabolism and Molecular Physiology of Saccharomyces cerevisiae , pp. 209-275. Edited by J. R. Dickinson & M. Schweizer. London:Taylor & Francis.
  32. Switzer, R. L. ( 1969; ). Regulation and mechanism of phosphoribosylpyrophosphate synthetase. I. Purification and properties of the enzyme from Salmonella typhimurium. J Biol Chem 244, 2854-2863.
    [Google Scholar]
  33. Switzer, R. L. & Sogin, D. C. ( 1973; ). Regulation and mechanism of phosphoribosylpyrophosphate synthetase. V. Inhibition by end products and regulation by adenine diphosphate. J Biol Chem 248, 1063-1073.
    [Google Scholar]
  34. Taira, M., Iizasa, T., Shimida, H., Kudoh, J., Shimizu, N. & Tatibana, M. ( 1990; ). A human testis-specific mRNA for phosphoribosyl-pyrophosphate synthetase that initiates from a non-AUG codon. J Biol Chem 265, 16491-16497.
    [Google Scholar]
  35. Tatibana, M. ( 1995; ). Mammalian phosphoribosyl-pyrophosphate synthetase. Adv Enzyme Regul 35, 229-249.[CrossRef]
    [Google Scholar]
  36. Wach, A., Brachat, A., Pohlmann, R. & Philippsen, P. ( 1994; ). New heterologous modules for classical or PCR-based gene disruptions in Saccharomyces cerevisiae. Yeast 10, 1793-1808.[CrossRef]
    [Google Scholar]
  37. Wach, A., Brachat, A., Alberti-Segui, C., Rebischung, C. & Philippsen, P. ( 1997; ). Heterologous HIS3 marker and GFP reporter modules for PCR-targeting in Saccharomyces cerevisiae. Yeast 13, 1065-1075.[CrossRef]
    [Google Scholar]
  38. Wente, S. R., Rout, M. P. & Blobel, G. ( 1992; ). A new family of yeast nuclear pore complex proteins. J Cell Biol 119, 705-723.[CrossRef]
    [Google Scholar]
  39. Whitters, E. A., McGee, T. P. & Bankaitis, V. A. ( 1994; ). Purification and characterization of a late Golgi compartment from Saccharomyces cerevisiae. J Biol Chem 269, 28106-28117.
    [Google Scholar]
  40. Wittenberg, C., Richardson, S. L. & Reed, S. I. ( 1987; ). Subcellular localization of a protein kinase required for cell cycle initiation in Saccharomyces cerevisiae: evidence for an association between the CDC28 gene product and the insoluble cytoplasmic matrix. J Cell Biol 105, 1527-1538.[CrossRef]
    [Google Scholar]
  41. Zinser, E. & Daum, G. ( 1995; ). Isolation and biochemical characterization of organelles from the yeast Saccharomyces cerevisiae. Yeast 11, 493-536.[CrossRef]
    [Google Scholar]
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