38. BIOSYNTHESIS OF PROTEINS IN BACTERIAL CELLS 431 



to ultraviolet irradiation may lose their capacity to give colonies on solid 

 media while still retaining their ability to increase in size. Investigations 

 have therefore been made to determine whether protein synthesis is possible 

 in the absence of DNA synthesis. 



The most useful system for this purpose is probably the mutant of E. 

 coli (strain 15T) discovered by S. S. Cohen 125 which exhibits a specific re- 

 quirement for thymine. When maintained in a minimal mineral medium 

 containing a source of energy, this organism does not synthesize DNA to 

 a significant extent (3% of the normal rate) but still produces adequate 

 amounts of protein and RNA. In addition, thymine starvation does not 

 prevent the induction of various enzymes (xylose isomerase 126 and /3-galac- 

 tosidase 127 ). It appears, therefore, that the organization of polypeptides 

 into a specific protein does not require DNA replication. 



Similar conclusions have been obtained by the use of several inhibitors 

 (proflavine, 127 nitrogen mustard, 127 " 130 ultraviolet- or X-irradiation 131 ■ 132 ) . 

 In all cases the system of DNA replication appears to be more sensitive 

 than that involved in protein or enzyme formation. 



Protein and RNA synthesis without concomitant DNA synthesis (a 

 situation depicted by S. S. Cohen under the term "unbalanced growth") 

 is generally lethal. 125 This lethal effect is related to changes in the ratio 

 protein/DNA rather than the ratio RNA/DNA. Thus, on the one hand, 

 RNA synthesis without concomitant synthesis of protein and DNA does 

 not give rise to the death of the bacteria 133 ; on the other hand, E. coli during 

 thymine starvation does not die if protein synthesis is blocked by an inhib- 

 itor (5-methyltryptophan). 125 It is not known why protein formation when 

 not accompanied by DNA synthesis should be a lethal process. 



During unbalanced growth however, the DNA exhibits some instability, 

 since the rate of spontaneous mutation is much higher amongst the sur- 

 vivors than in the population supplemented with thymine. 134, 135 In addition 

 starvation for thymine favors the synthesis of atypical bases. 136 



125 S. S. Cohen and H. D. Barner, Federation Proc. 13(1), (1954). 



126 S. S. Cohen and H. Barner, J. Bacteriol. 69, 59 (1958). 



127 F. Gros-Doulcet, F. Gros, and S. Spiegelman, 3rd Intern. Congr. Biochem., Brus- 

 sels, 1955 p. 74 (1956). 



128 A. B. Pardee, Proc. Natl. Acad. Sci. U. S. 40, 263 (1954). 



129 R. M. Herriot, J. Gen. Physiol. 34, 761 (1951). 



130 E. I. Sher and M. F. Mallette, Arch. Biochem. Biophys., in press, quoted by Spie- 

 gelman. 146 



131 A. Kelner, J. Bacteriol. 65, 252 (1953). 



132 L. S. Baron, S. Spiegelman, and H. J. Quastler, /. Gen. Physiol. 36, 631 (1953). 



133 E. Borek, A. Ryan, and J. Rockenbach, J. Bacteriol. 71, 318 (1956). 



134 R. Weinberg, and A. B. Latham, J. Bacteriol. 72, 570 (1956). 



135 C. A. Coughlin and E. A. Adelberg, Nature 178, 531 (1956). 



136 D. B. Dunn and J. D. Smith, Nature 175, 336 (1955). 



