352 MAHLON B. HOAGLAND 



concept: it has since been shown 21 that the amino acid was attached to RNA, 

 not protein.) All evidence available to date appears clearly to support the 

 simple concept that when a free amino acid enters a protein by way of 

 coupling with an endergonic process, it does so by de novo synthesis of pro- 

 tein (i.e., a polypeptide chain has increased in length by one amino acid) 

 and when it leaves it does so by degradation of the same chain. 



II. Participation of Cellular Nucleic Acid-Containing Fractions 

 in Protein Synthesis 



Over the past two decades evidence has accumulated which points to an 

 intimate association between cellular nucleic acid and protein synthetic 

 activity. This evidence has been thoroughly reviewed recently (cf. particu- 

 larly Brachet 1 and more recently Chantrenne 8 ) . The highlights along this 

 road should be briefly mentioned. Brachet and Caspersson were the first 

 to point to this association. A large number of studies, stemming from Bra- 

 celet's early experiments and the more recent work of Gale and Folkes 19, 20 

 in bacterial systems, have shown that ribonuclease disrupts the cell's pro- 

 tein synthetic machinery and that ribonucleic acid (RNA) can frequently 

 restore it. Studies on bacterial transformation 22 ' 23 and the discovery of the 

 autonomous infectivity of tobacco mosaic virus RNA 24 ' 25 unequivocally 

 establish that DNA and RNA alone contained the necessary information 

 in their structure to direct the synthesis of new and genetically specific 

 proteins. A large body of information on the fate of C 14 -amino acids in 

 whole animals, as we shall see below, demonstrated conclusively that the 

 initial and major site of incorporation of amino acids into protein were the 

 cellular ribonucleoprotein particles or ribosomes. Thus it was clear, before 

 cell-free systems had received much scrutiny, that nucleic acid had some 

 intimate directive role in converting amino acids to protein. We shall now 

 consider in detail the various major nucleic acid-containing cellular com- 

 ponents and examine the evidence, based on the more direct in vitro studies, 

 for the role of each of these fractions in protein synthesis. In the sections 

 to follow only those experiments which seem to bear directly on the par- 

 ticipation of nucleic acids have been considered. 



21 E. F. Gale, in "Recent Progress in Microbiology" (G. Tunerall, ed.). Almquist 

 and Wiksel, Stockholm, 1959. 



22 O. T. Avery, C. M. MacLeod, and M. McCarty, J. Expll. Med. 79, 137 (1944). 



23 R. D. Hotchkiss, in "The Chemical Basis of Heredity" (W. D. McElroy and B. 

 Glass, eds.), p. 321. Johns Hopkins Press, Baltimore, 1957. 



24 A. Gierer and G. Schramm, Nature 177, 702 (1956). 

 26 H. Fraenkel-Conrat, J. Am. Chem. Soc. 78, 882 (1956). 



