198 KARL G. LARK 



initiatin^ij; DXA biosynthesis, and that rcjjicssion of ccrlain cnzynics may 

 lead to a lack of such synthesis. In correhiting the production of DNA 

 precursors with DNA biosyntiiesis two rehitionships may be encountered: 

 The first, which may exist in germinal and embryonic tissue, could 

 involve the induction of a metabolic pathway as a result of accumulation 

 of large quantities of DNA precursors. Tn this situation, the sudden 

 IM-oduction of precursor may set in motion a train of events leading to 

 the initiation of DNA biosynthesis. The second, which may exist in cells 

 from adult organisms, in vegetative cells, and in bacteria, is one in which 

 prochiction of precursors occurs as a result of derepression and the 

 machinery for producing DNA precursors is eitlier synthesized or acti- 

 vated upon demand. The two systems differ only in that in the first, a 

 stimulus applied at one end of the reaction chain forces biochemical 

 events toward initiation of biosynthesis, whereas in the second, the 

 initiation of biosynthesis forces a need for mechanisms which supply the 

 necessary precursor materials. In both cases the mechanism for supply- 

 ing the necessary precursors may be the same; however, in the first this 

 mechanism may act as stimulus to initiate biosynthesis. 



In no case, however, can such mechanisms exercise more than a crude 

 control over the synthesis of DNA. It is impossible to explain the 

 termination of synthesis and its reinitiation with no api)arent disap- 

 pearance of the enzymatic mechanisms evoked. Nor can the stoichi- 

 ometry of DNA biosynthesis, resulting in the exact duplication of all of 

 the material initially present, be accounted for. Finally, the rather 

 specific pattern of time at which individual chromosomes are duplicated 

 (discussed in Chapter II) cannot be controlled by such a mechanism. 



An additional, more intimate and precise control appears to be 

 operative which is capable of providing the stimulus for activating the 

 machinery for precursor production. 



The role of the primer in maintaining such a control is very attrac- 

 tive, but has yet to be investigated in vivo. Nevertheless, it would appear 

 that it could play an all-important role in the control of biosynthesis; a 

 compelling reason for assuming this, is that it is only at this level that 

 the stoichiometry of DNA synthesis could be controlled. 



Any controlling role of the DNA molecule in its own biosynthesis 

 would appear to be complex indeed. The experiments discussed in Sec- 

 tions III and IV above would indicate that, among other things, the 

 interaction of this macromoleculc with others such as RNA and protein 

 will play an im]:)ortant role in determining its availability to act in its 

 own biosynthesis. Before such a mechanism can be established, experi- 

 ments must be carried out on in vivo systems to establish the existence 

 of a primer state and a means of quantitating its jiarticipation in bio- 



