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the absence of the metabolite they reqiiire, and the same is true for ademne ess 

 mutants Further, growth of uracilless and adenineless mutants under limiting 

 conditions of the required metabolite, leads to the temporary loss of enzyme- 

 synthesizing ability even in the presence of the metabolite they need. 



CARTER: Could that mean that the uracil polyphosphate or adenine 

 coenzymes could be implicated as well as ribose nucleic acid? 



SPIEGELMAN: I don't think so. Well, it could, yes. 



CARTER: So, in other words, it may turn out to be a low molecular 

 weight compound that takes us out of this holy trinity. 



MAZIA: Except that this synthesis has to impart specificity, and 

 therefore the substance has to be a nuclear product. 



CARTER: He emphasized that it does not have to be a nuclear product. 



SPIEGELMAN: What do you mean? There is no evidence in these ex- 

 periments that you need nuclear products continually made by the nucleus. 



MAZIA: No, but there was a nucleus there. 



CARTER: It is a cell, in other words. 



SPIEGELMAN: If it does not have the right gene, for example, it 

 does not do any good. 



CARTER: But it does not have a nuclear apparatus in this experiment 

 that you are talking about. 



MAZIA: But it has had one. It may still be operative via the specific 

 products it has put into the cytoplasm. 



SPIEGELMAN- The possibility that nucleotides and their phosphory- 

 lated derivatives are involved in some generalized and nonspecific fashion in the 

 experiments that I described, is an important one to consider. Certainly for 

 example, the complete depletion in the cell of adenylic acid and its derivatives 

 would completely abolish all activities, including enzyme synthesis. We have 

 attempted to get around this difficulty by adjusting our treatments as well as our 

 inhibitory agents, so as not to interfere with overall metabolic processes. In- 

 deed, we have been quite lucky in being able to adjust the level of antagomst so 

 that there was actually no interference with growth. Nevertheless, we were able 

 to exhibit a specific interference with the synthesis of a particular enzyme. 

 This specificity is due to the fact that the forming system involved was a poor 

 competitor for the nucleotides. We have subsidiary evidence supporting the 

 conclusion which I cannot detail now. 



It might perhaps, be of interest to note some other experiments with 

 yeast which provide relevant information. We discovered the existence in yeast 

 of a nucleotide pool quite analogous to the free amino acid pool with which we 

 had been dealing in the past few years. It may be remembered that with the free 

 amino acid pool we were able to show that suppression of the mcorporation of 

 any one of the free amino acids led to the cessation of enzyme synthesis. We 

 were able to devise procedures whereby we could deplete the nucleotide pool in 

 the cell and examine the consequence for enzyme formation. This was accom- 



