IV. CELLULAR CONTROL OF DNA BIOSYNTHESIS 181 



Cultures of synchronized bacteria {Alcaligenes faecalis), in which 

 DNA synthesis occurs in steps, will cease to synthesize DNA if large 

 amounts of deoxyadenosine are added to the medium (presumably as a 

 result of precursor starvation; see Section II.A). If this is done immedi- 

 ately before a burst of DNA synthesis (to cells which presumably have 

 completed all the necessary preparations for DNA synthesis) DNA 

 synthesis is blocked. Reversal of inhibition at different periods there- 

 after leads to an eventual resumption of DNA synthesis which occurs 

 during a period in which a control (non-inhibited) culture undergoes a 

 second cycle of DNA synthesis. The timing at which this eventual DNA 

 synthesis takes place is independent of when inhibition is initiated or 

 reversed (Lark, 1960), and is illustrated in Fig. 9. Non-synchronized 

 exponential cultures of this organism treated in this way initiate DNA 

 synthesis immediately upon reversal of inhibition and proceed to synthe- 

 size DNA exponentially at the normal rate. These results have been 

 interpreted as evidence for the existence of certain allowed periods of 

 DNA synthesis. The lack of correspondence between these periods and 

 the periods for which DNA precursor production is inhibited led to the 

 suggestion that control of these periods depended upon the conversion of 

 DNA to a primer state rather than upon the production of precursor 

 material. This was further emphasized by the finding that DNA pre- 

 cursors, when added to the growth medium, could only influence the 

 DNA cycle if added during an allowed period of synthesis. 



Cultures of E. coll starved of an essential amino acid cease produc- 

 tion of DNA. Ability to synthesize this macromolecule is regained upon 

 readdition of the essential amino acid. Reacquisition of this synthetic 

 ability is inhibited by both chloramphenicol and irradiation. Extracts of 

 cells so inhibited exhibit adequate activity of all of the enzymes neces- 

 sary to synthesize DNA (Billen, 1962b) . The lack of in vivo synthesis has 

 been interpreted as an inability of intracellular DNA to enter into the 

 primer state. 



The slime mold Physarum polycephalum undergoes synchronized 

 mitosis. Guttes and Guttes (1961) studied the ability of a "well-fed" 

 Plasmodium to support DNA synthesis in an implanted plasmodium 

 which had been previously starved. DNA synthesis in the former took 

 place 3-4 hours after mitosis, whereas in starved plasmodia it occurs 

 after 6-9 hours. If a starving plasmodium was implanted into one which 

 was well fed at a period in which neither was synthesizing DNA, the 

 well-fed Plasmodium could initiate and support DNA synthesis of the 

 implant despite the fact that it was not itself synthesizing DNA. They 

 interpreted their results to indicate that DNA synthesis in the well-fed 

 plant was controlled by some factor other than the substrate and enzyme 

 conditions required for DNA synthesis and suggested that the ability of 



