IV. CELLULAR CONTROL OF DNA BIOSYNTHESIS 197 



E. THE DISSOCIATION OF THE CELL DIVISION CYCLE FROM DNA SYNTHESIS 



We have already noted the use of inhibitors to study the dependence 

 of DNA synthesis on precursor production (Section II) or on synthesis 

 of protein and RNA (Sections II and IV). Such experiments have also 

 proved extremely useful in studying the dissociation of DNA synthesis 

 from mitosis, or cell division. 



Mercaj^toethanol has been used to block the development of centrioles 

 in fertilized sea urchin eggs, an event known to precede DNA synthesis. 

 Nevertheless, DNA synthesis (if the agent is added in interphase) will 

 proceed (Bucher and Mazia, 1960). On the other hand, if cells in meta- 

 phase are blocked by this agent, DNA synthesis is also blocked, indi- 

 cating that DNA in the condensed form of the metaphase chromosome 

 cannot duplicate. In this case, an interesting phenomenon may occur. 

 The centers divide and form a quadripolar figure and upon the release 

 of inhibition the egg divides into four, each of the nuclei receiving only 

 half of its normal complement of DNA. Nevertheless, this appears to 

 be adequate since such cells go on to further division and development. 

 The DNA deficiency is made up before the next division since the cells 

 go through a cycle in which the required number of centriolar units are 

 restored (Mazia, 1960). It would be of interest to know whether the 

 DNA so made, is made in two cycles of normal duration, including Gi, 

 S, and G\.. or whether the cell immediately replenishes the necessary 

 material in one big step. 



As pointed out in this section (see Section V,B and C), under certain 

 conditions, both temperature and nutritional changes can be used to 

 dissociate the cell division cycle from DNA synthesis. Similarly, inhibi- 

 tors of protein synthesis in bacteria may block cell division while allow- 

 ing a DNA cycle to proceed (Maruyama and Lark, 1961), whereas an 

 inhibitor of DNA synthesis (deoxyadenosine) will block DNA synthesis 

 while permitting a further cycle of cell division (Lark, 1960). 



Finally, repeated observations of synchronous cultures have shown 

 that cycles of cell division and DNA synthesis may often be dissociated 

 under conditions of continued cell growth and proliferation (Lark, 1962). 



VI. Summary, Conclusion, and Opinions 



To date, the most complete body of experimental results concerning 

 the regulation of DNA biosynthesis has been concerned with the role of 

 precursors. From the data described above, there seems to be little doubt 

 that production of DNA precursors may act as part of a mechanism for 



