IV. CELLULAR CONTROL OF DNA BIOSYNTHESIS 199 



synthesis. At present such experiments involve measurements carried 

 out on material which has been extracted from cells in a given state of 

 growth or division. However, the present state of microspectrophoto- 

 metric techniques suggests that it may be possible to carry out physico- 

 chemical investigations of macromolecules in situ. If a role of primer in 

 controlling biosynthesis can be established, the problems of the control 

 of DNA biosynthesis will have only begun. It will then be necessary to 

 establish the mechanisms whereby non-replicating material is converted 

 to the primer state. The experiments discussed indicate that both protein 

 and RNA synthesis may play an important role in this respect. The 

 state of the template which directs RNA and protein synthesis may 

 depend upon its interaction with these macromolecules. Moreover, it ap- 

 pears that DNA biosynthesis requires concomitant histone biosynthesis. 

 The timing of DNA biosynthesis appears to depend upon the termina- 

 tion of the previous period during which synthesis could take place. This 

 suggests that some "timing reaction" is initiated upon cessation of DNA 

 synthesis or upon cessation of a particular state ("primer") associated 

 with DNA biosynthesis. The existence of such a reaction remains to be 

 either proved or disproved, but the ability of chemical and physical 

 changes in the environment to affect the DNA cycle of different cells to 

 different extents suggests that such a mechanism exists and may be 

 operative during G^ but not during S, the period of DNA synthesis. A 

 possible mechanism has been suggested in Section IV,A above. 



The above conclusions concern intracellular control mechanisms 

 operating at the molecular level. However, it is obvious that these in 

 turn must be affected by the external environment of the cell and by its 

 internal structure. The experiments discussed in Section V are only a 

 small sample of the data available. However, they serve to illustrate the 

 complexity of this problem. Within the cell, molecular components of 

 the control mechanism must be brought together. Changes in the environ- 

 ment, often produced by neighboring cells, may initiate or halt the 

 synthetic cycle. The period elapsing between mitosis and the onset of 

 DNA synthesis appears to be extremely important in deciding the 

 destiny of a cell. The most immediate effect of this decision may be the 

 ability to synthesize DNA. 



The significance of this aspect of the control of DNA biosynthesis 

 may, perhaps, be viewed as follows: A series of molecular events within 

 the cell control the functioning and duplication of DNA in a precise 

 manner. The result of this control will determine whether the capacities 

 of the cell are directed toward some particular purpose, other than 

 duplication, or to replication of the cell itself. Changes produced by 

 the interaction of the cell and its environment may be influential in 



