STRUCTURAL AND CHEMICAL ARCHITECTURE OF HOST CELLS 97 



As indicated above, in discussing the effect of dicUorobenzimidazole 

 riboside on protein syntliesis in nuclei or the inhibitory effect of ribonuclease 

 on protein synthesis in amoebae, the integrity, synthesis, or metabohsm of 

 RNA and the component nucleotides is intimately tied to protein synthesis. 

 However, a precise analysis of the mechanism of various compounds on 

 protein synthesis is difficult to obtain with intact cells. Since it is known that 

 all of the ribose nucleotides fomid in RNA may act as coenzymes in various 

 phases of intermediary metabolism, it is difficult to be certain that inhibitory 

 analogs of RNA components are carrying out their primary effect on RNA 

 synthesis. For example, high energy phosphate is presumably essential to 

 protein synthesis. Does dichlorobenzimidazole riboside inhibit synthesis of 

 ATP, RNA synthesis, or both? Uracil -deficient organisms are usually unable 

 to synthesize protein. However, in at least one instance uracil deficiency in 

 bacteria markedly inhibited respiration (Cohen and Earner, 1955). In this 

 system the significance of a concomitant inhibition of RNA and protein 

 synthesis is obscured by the fact that the synthesis of these polymers is tied 

 to energy production. 



An analysis of the precise mode of action of analogs of nucleic acid com- 

 ponents presents problems similar to those seen with amino acid analogs. 

 As will be discussed below, analogs of purines and pyrimidines may or may 

 not enter intermediates in nucleic acid metabohsm or into the nucleic acids 

 themselves, resulting in the production of more or less damaged nucleic acids 

 or the inhibition of nucleic acid biosynthesis. 



V. Protein Synthesis and the Nucleic Acids. It may be asked whether 

 existing data on intact cells indicate that protein synthesis is tied either to 

 the presence of RNA or to its synthesis. An excellent recent survey of these 

 data is that of Borsook (1956). It has been reported that mature rabbit 

 erythrocytes contain about 4 % RNA and are unable to synthesize protein 

 (Hollo way and Ripley, 1952), thereby indicating the existence of other 

 controlling factors, as indicated in the discussion of enucleate cells. 



In the course of erythropoiesis, hemoglobin appears most rapidly when 

 cytoplasmic nucleic acid has almost disappeared (Hammarsten et al., 1953). 

 However, it can be suggested that this very decrease in RNA content is 

 linked in some way to the synthesis of protein. An alternative hypothesis 

 suggests that a small fraction of the RNA is undergoing a rapid turnover, 

 thereby permitting a concomitant RNA synthesis and protein synthesis 

 (Kruh and Borsook, 1955). Some unequivocal evidences of such RNA turn- 

 over are now known. For example, although some years ago it appeared that 

 protein synthesis in T2 -infected bacteria occurred without RNA synthesis 

 (Cohen, 1947), it has been fomid that a rapid RNA synthesis and turnover 

 occurs in a small fraction (1 to 3 %) of the total RNA of the infected ceU 

 (Volkin and Astrachan, 1957). 



