102 S. S. COHEN 



protein synthesis. However, not all data support the concept of a compulsory 

 coupling of the two functions. Hotchkiss (1956) has shown that, in resting 

 staphylococci, the uptake of P^^ into nucleic acid was inversely related to 

 the rate of protein synthesis. In an unusual auxotrophic mutant of E. coli, 

 requiring methionine, ENA accumulated mider conditions of methionine 

 starvation (Borek et al., 1956). No other amino acid-requiring mutant has been 

 observed to react in this way; in aU other auxotrophs the cessation of protein 

 synthesis as a result of amino acid deficiency also prevents RNA synthesis. 



Of particular interest in this regard is the action of the antibiotic, chlor- 

 amphenicol or Chloromycetin, which at suitable concentrations inliibits 

 protein sjmthesis in bacteria up to 2 to 5 % of the normal value (Gale and 

 Folkes, 1953; Wisseman et al., 1954). Despite this marked inhibition, nucleic 

 acid synthesis proceeds actively. A similar result has been effected with 

 cobalt (Levy et al., 1949). Chloramphenicol has been a powerful tool in the 

 study of nucleic acid metabolism in phage-infected bacteria, as described by 

 Tomizawa and Sunakawa (1956) and by Hershey and Melechen (1957), who 

 showed that, by the judicious use of the antibiotic at an early stage of in- 

 fection, one may block the synthesis of a protein essential to the production 

 of phage DNA. This result had also been obtained by other techniques, such 

 as the use of amino acid-deficient mutants (Burton, 1955) or amino acid 

 analogs (Cohen and Fowler, 1947). By blocking protein synthesis at a later 

 stage of infection, it was possible to accumulate viral nucleic acid (DNA) 

 under conditions in which the production of viral protein was either negligible 

 or at least very markedly reduced. In addition, the presence of chloram- 

 phenicol exaggerates UNA synthesis in virus-infected bacteria. 



Bacteria were permitted to accumulate RNA in the presence of chloram- 

 phenicol and their extracts have been compared electrophoreticaUy with 

 extracts of normal organisms (Pardee et al., 1957). A new nucleoprotein 

 component, which was relatively nonsedimentable in contrast to the S40 

 component, was detected by electrophoresis in the extract of chloramphen- 

 icol-treated bacteria, i.e., the newly accumulated RNA did not exist in the 

 free state. On sonic vibration this nucleic acid was released in the free state 

 from the new nucleoprotein fraction, unlike normal RNA which was not thus 

 readily released from the S40 component. 



Despite these results, Gros and Gros (1956), and Pardee and Prestidge 

 (1956) have asked whether RNA synthesis does not still at least require the 

 presence of amino acids. Both groups have shown that chloramphenicol did 

 not permit RNA synthesis in amino acid-deficient bacterial mutants nor did 

 bases accumulate in the organism. However, the addition of traces of the 

 required ammo acids now permitted extensive RNA synthesis. Gros and Gros 

 (1956) have observed that if the amino acid is added after the antibiotic, 

 RNA synthesis starts but not that of DNA. The RNA's made in the presence 



