IV. CELLULAR CONTROL OF DNA BIOSYNTHESIS 173 



is blocked (Bolluni ct ciL, 1960). Thus, it appears that with respect to 

 radiosensitivity, at least two possible control steps may be differentiated, 

 one of which does not involve the enzymatic production of precursors. 

 It is not known whether both are operational in non-irradiated cells. 



III. Role of Protein or RNA Synthesis in 

 Controlling DNA Synthesis 



The relative synthesis of RNA, DNA, and protein within growing 

 cells has been studied with increasing intensity in recent years. Such 

 studies have stressed the importance of the interrelationship between 

 the synthesis of different types of macromolecules. Several studies have 

 been carried out attempting to elucidate the role that protein or RNA 

 synthesis may play in the synthesis of DNA. 



It is obvious that protein synthesis must be maintained in dividing 

 cells if each cellular unit is to receive a sufficient complement of enzymes 

 to function properly. Absence of certain enzymes, as we have seen in 

 the preceding section, may help to account for the lack of DNA synthe- 

 sis in certain situations. This may be the case in systems such as 

 regenerating liver and the microspores of the lily anther (discussed 

 above), which are unable to synthesize DNA and may be induced to 

 regain this capacity. Although experiments with such systems are illus- 

 trative of a possible control mechanism, it is questionable whether cells 

 which are rapidly dividing and synthesizing DNA lose the enzymes 

 controlling DNA synthesis during the non-synthetic portion of the DNA 

 cycle. 



Measurements of the persistence of such enzyme systems in bacteria 

 have shown their presence, in adequate amounts, in cells in which 

 protein or DNA synthesis, as well as cell division, have been blocked 

 for periods greater than a division cycle (Billen, 1960a; Doudney and 

 Billen, 1961; Billen, 1962a). In a synchronized bacterial system, exhibit- 

 ing periodic DNA synthesis, enzymes which convert thymidine mono- 

 phosphate into thymidine triphosphate double in activity during a 

 defined, short period of the division cycle. Although this increase in 

 activity does not occur in the presence of chloramphenicol, cyclic DNA 

 synthesis persists and enzyme activity is maintained (Maruyama and 

 Lark, unpublished data). 



In contrast to these findings, work with plants and animal cells has 

 shown that enzymatic activity may disappear during a period of several 

 days (or a few generations) and that some enzymes may be lost more 

 easily than others. Thus, upon transfer of HeLa or L cells to fresh 

 medium, the intracellular activities of thymidine kinase, thymidylic 

 kinase, and thymidine diphosphate kinase increase sequentially (Weiss- 



