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

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Abstract
When plated in medium containing 0.5 μg/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, wildtype 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 adenosineresistant mutants that behaved as PRPP “overproducers.” These mutations conferred partial resistance to various toxic purine and pyrimidine analogs and preserved HGPRT activity in adenosinecontaining 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.