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The control of cell proliferation by preformed purines: a genetic study. II. Pleiotropic manifestations and mechanism of a control exerted by adenylic purines on PRPP synthesis.

Abstract
When plated in medium containing 0.5 microgram/ml coformycin and adenosine (or adenine) fibroblasts were killed, even if pyrimidines were supplied. Measurements of N-formylglycine amide ribonucleotide synthesis showed that lethality is a manifestation of purine starvation. In the case of adenosine kinase deficient cells, growth was restored by hypoxanthine. The adenylic derivatives block only purine biosynthesis, presumably by inhibition of PRPP-amidotransferase. In this same medium, wild-type cells exhibited symptoms of PRPP deprivation: purine and pyrimidine syntheses were both shut off and HGPRT was simultaneously inactivated. The pleiotropic control by adenosine was abolished in adenosine-resistant mutants that behaved as PRPP "over-producers." These mutations conferred partial resistance to various toxic purine and pyrimidine analogs and preserved HGPRT activity in adenosine-containing medium. This permits selection against these mutants. Evidence suggesting that adenosine kinase products may fulfill a specific function in the regulation of PRPP synthesis is discussed.
AuthorsM Debatisse, G Buttin
JournalSomatic cell genetics (Somatic Cell Genet) Vol. 3 Issue 5 Pg. 513-27 (Sep 1977) ISSN: 0098-0366 [Print] United States
PMID918825 (Publication Type: Journal Article)
Chemical References
  • Anti-Bacterial Agents
  • Azepines
  • Pentosephosphates
  • Ribonucleosides
  • Phosphoribosyl Pyrophosphate
  • Hypoxanthine Phosphoribosyltransferase
  • Adenosine Kinase
  • Adenine
  • Adenosine
Topics
  • Adenine (pharmacology)
  • Adenosine (pharmacology)
  • Adenosine Kinase (metabolism)
  • Anti-Bacterial Agents (pharmacology)
  • Azepines (pharmacology)
  • Cell Line
  • Hypoxanthine Phosphoribosyltransferase (metabolism)
  • Mutation
  • Pentosephosphates (biosynthesis)
  • Phosphoribosyl Pyrophosphate (biosynthesis)
  • Ribonucleosides (pharmacology)

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