154 KARL G. LARK 



biosynthesis of DNA are of interest in the study of pi'ohh'nis of (Uffer- 

 entiation as well as those studies concerned witli the maintenance of 

 genetic continuity, since absence of DNA synthesis may prevent, and 

 thus control, further cell division without impairing cell function. 



Individual cells possess the ability to control DNA synthesis. During 

 a normal cycle of cellular division the content of DNA, as measured 

 chi'mically and genetically, is exactly doubled. Tlie existence of this 

 situation has been inferred for some time from the knowledge that during 

 multiplication the DNA content of individual cells of a given species 

 or clone remains remarkably constant and that the chromosome number 

 of the vast majority of individuals arising in a clone also does not in- 

 crease or decrease. Instances in which a dividing cell divests itself of 

 genetic material as a result of asynchrony between cell division and 

 duplication of DNA are the exception rather than the rule; cells in which 

 DNA synthesis and cell division have ceased usually resume DNA 

 synthesis before division recommences. 



The extent to which intracellular DNA synthesis is controlled has 

 become apparent in recent years, tlirough use of cellular autoradiogra- 

 phy, quantitative microspectropliotometry, and synchronous culture 

 techniques. As a result of these studies it has become evident that most 

 animal, plant, or protozoan cells, as well as some bacteria, have a defined 

 period during their life cycle during which DNA is synthesized. 



The living cell therefore exhibits two types of control over the bio- 

 synthesis of DNA: one, quantitative; the other, temporal. The amount 

 synthesized is always equal to that initially present and the time of 

 synthesis is restricted to a defined interval during the division cycle. 



Although the evidence for this control of DNA synthesis has been 

 available for some time, few systematic attempts have been made to 

 understand the mechanism of control which governs the "DNA cycle." 

 This has been due, in part, to a natural desire for further evidence to 

 substantiate the generality of such a cycle and, in part, to a lack of 

 knowledge of the biochemical mechanisms underlying the synthesis of 

 DNA. Until recently, microscopic observation was found to be of little 

 use in studying the interphase nucleus, in which DNA is synthesized. 



In recent years the enzymatic basis for DNA synthesis has become 

 known, and work has concentrated upon the study of the in vivo 

 replication mechanism of this genetic material. In addition, physico- 

 chemical information on the structure of the molecule, spurred on by 

 the development of new physical techniques and genetic concepts, has 

 led to a detailed knowledge of its structure. 



Finally, a more detailed knowledge of the mechanisms whereby DNA 

 controls the svnthesis of cellular material has led to an ever-increasing 



