STRUCTURAL AND CHEMICAL ARCHITECTURE OF HOST CELLS 127 



of the analog of the base present m DNA, there is a very considerable replace- 

 ment of the original base. Data on the shape of the replacement curve, 

 particularly in the early periods, are not available and it is important to be 

 sure that the phenomenon does not arise from ceUular turnover within a 

 population of labile cells. 



This experiment is so important that it is certam that this question will be 

 clarified in the near future. In addition to providing a major exception to the 

 concept of DNA stabihty, it raises the possibility that the induction of 

 thymine deficiency in some way labilizes the DNA chain. The phenomenon 

 may assist m explaining thymineless death in bacteria and may prove to be 

 a phenomenon of potentially great significance in approaching problems of 

 chemotherapy. Such a labilization may also be of considerable interest 

 in the study of mutation, as suggested by Coughlin and Adelberg (1956) 

 and may suggest an added role for the ubiquitous RNAase and 

 DNAase. 



It may be suggested that the experiments so far constructed to test the 

 metabohc activity of the nucleic acids are vaUd only if complete imits, e.g., 

 nucleotides, are added or removed. Even as protems may possess several 

 polypeptide chains, the nucleic acids are not known to exist in biological 

 materials as single polynucleotide chains. In DNA, bases are bonded together 

 so that each nucleotide is held in three ways, including the two phospho- 

 diester bonds of the internucleotide linkage. In RNA, bases may also be 

 bonded to other bases or possibly to protein. Thus the possibility exists that 

 internucleotide bonds may be cleaved without disrupting polynucleotide 

 chains. If, as we beHeve hkely as a result of enzyme studies to be discussed 

 in a later section, these cleavages are phosphorylytic and involve the forma- 

 tion of pyrophosphate bonds which may be exchanged with amino acids to 

 give phosphocarboxyanhydrides, a mechanism is available for organizing 

 amino acids selectively at nucleic acid templates as a preliminary step to 

 peptide synthesis. The release of such an anhydride-bound amino acid may 

 permit a concomitant closing of the phosphodiester bond, as in Fig. 25. In 

 such a sequence the nucleic acids may be intensely active and would show no 

 evidence of phosphorus, nitrogen, or carbon replacement. Indeed, it is not 

 immediately evident that one could expect a turnover of oxygen in the sys- 

 tem, although this can certainly be tested. Although some information is 

 available concerning the phosphorylytic cleavage of RNA and the pjTO- 

 phosphorylytic cleavage of DNA, and the attachment of an amino acid m 

 such a fragment has recently been recorded, the nature of amino acid 

 transfer to nucleic acid and of amino acid acceptors is entirely hypothetical 

 and is presented only to complete a possible mechanism of nucleic acid 

 activity which may operate without detectable turnover in the atoms so far 

 examined. 



VOL. I — 10 



