162 KARL C. LARK 



\iy ciitcriiiu; a |)riiiu'r slate DXA may initiate its own i-eplicatioii 

 which may again be terminated when primer is no longer avaihible. 

 During DNA replication the conversion to primer may l)e a complicated 

 process which may involve structural changes in the molecule itself and 

 in its association with other molecules such as protein and KNA. 



At this level, then, control of DNA biosynthesis may involve the 

 synthesis of RNA or protein or both. 



Finally, it should l)e realized that restrictions on the proximity of 

 the various components of the polymerizing reaction may play an 

 important role. Thus, if the various enzymes involved in DNA synthesis 

 (kinase and polymerase) are formed in the cytoi)lasm, they must enter 

 the nucleus in order to utilize the DNA primer. 



II. Role of DNA Precursors in Controlling DNA Synthesis 



In order to synthesize DNA the cell nuist produce the necessary pre- 

 cursor deoxyribotides. In vitro enzymatic studies have shown that these 

 must be present in the triphosphate form and that all of the nucleotides 

 found in the DNA which is being synthesized must be present simul- 

 taneously. There is eveiy reason to believe that the results of these 

 studies are valid in vivo as well as in vitro. 



For example, bacteria, upon infection with bacteriophage, commence 

 the rapid production of large quantities of viral DNA which continues 

 until the cell lyses (Cohen, 1947; Hershey et al, 1953). It has been 

 shown that a primaiy step in the conversion of the cell into such a 

 "DNA factory" is the production of many new enzymes needed for the 

 synthesis of new types of phage-specific deoxynucleotides (Flaks and 

 Cohen, 1957; Kornberg et al., 1959), as well as the production of 

 increased quantities of pre-existing enzymes also associated with DNA 

 synthesis. All of these are necessary for producing the deoxynucleotide 

 triphosphates required for DNA synthesis. As would be expected, such 

 phage-infected cells contain large quantities of acid-soluble purine and 

 pyrimidine deoxynucleotides, whereas uninfected cells contain small 

 amounts of only the pyrimidine deoxynucleotides (O'Donnell et al., 

 1958). Moreover, to further enhance the efficiency of the system the 

 enzymatic balance of the cell is shifted to emphasize the synthesis of 

 DNA rather than RNA (Cohen, 1947). Although this system may be 

 regarded as one in which DNA synthesis continues "out of control" 

 it exemplifies a biological system in which the cell follows the predictions 

 of the enzyme chemists, with respect to precursor production and DNA 

 biosynthesis. 



Granted that the production of DNA pi-ecursors is a necessary step 



