432 F. GROS 



A direct application of the uncoupling of DNA and RNA synthesis will 

 be discussed later in relationship to experiments based on the decay of P 32 

 in bacteria labeled in their nucleic acids. 



2. Protein Synthesis in the Absence of RNA Synthesis, or during 

 Formation of an Atypical RNA 



As will appear in the general discussion, one of the most commonly 

 accepted hypotheses concerning the relationships between RNA and pro- 

 tein is that protein formation depends on RNA synthesis. In other words, 

 the RNA would serve only once as a template for protein formation instead 

 of acting as a catalyst in the process. 



This hypothesis is derived mostly from experiments in which attempts 

 have been made to dissociate protein and enzyme formation either from net 

 RNA synthesis (by using purines or pyrimidine mutants) or from the 

 synthesis of chemically normal RNA (by the use of base analogs). 



a. Studies with Mutants 



Contrary to what is observed during thymine starvation, specific starva- 

 tion for uracil in E. coli leads to complete cessation of growth and does not 

 permit the induction of /3-galactosidase. 137, 138 This is generally interpreted 

 as proof that protein synthesis, and especially synthesis of specific protein, 

 requires the concomitant synthesis of RNA. 



This interpretation may have to be modified however in the light of the 

 experiments of Magasanik et al. 139 on the control of enzyme synthesis in 

 bacteria. Using a mutant of Aerobaeter aerogenes which requires guanine, 

 they observed that bacteria deprived of guanine can synthesize large 

 amounts of certain enzymes, the nature of which depends on the carbon 

 source. For instance, when maintained on inositol in the absence of guanine, 

 the bacteria can synthesize inositol dehydrogenase and inosinic dehydrogen- 

 ase; if instead of inositol, glycerol, histidine, or glucose are added, the bac- 

 teria synthesize the inosinic dehydrogenase but not the inositol dehydro- 

 genase. 



These results can be explained by the well-known phenomenon of enzyme 

 repression. If one supposes that deprivation of guanine considerably retards 

 growth for a reason which may be independent of the cessation of nucleic 

 acid synthesis, it is clear that since the bacterium metabolizes the carbon 

 source, it will accumulate large pools of endogenous repressors; the synthe- 



137 J. Monod, A. M. Pappenheimer, and G. Cohen-Bazire, Biochim. et Biophys. Acta 

 9, 648 (1952). 



138 A. B. Pardee, Proc. Natl. Acad. Set. U. S. 40, 263 (1954). 



139 B. Magasanik, A. K. Magasanik, and F. C. Neidhardt, in "The Regulation of Cell 

 Metabolism," A. Ciba Symposium, p. 334. Churchill, London, 1959. 



