IV. CELLULAR CONTROL OF DNA BIOSYNTHESIS 169 



is not preceded by a rapid increase in intracellular deoxyribosidic 

 compounds (Lark, 1961). 



Okazaki has shown that the major components of the deoxynucleo- 

 tide pool in E. coll do not normally serve as an immediate precursor for 

 the bulk of the intracellular DNA. Thus, labeled thymidine incorporated 

 into thymidine diphospho sugar compounds does not turn over as rapidly 

 as thymidine mono-, di-, or triphosphates (Fig. 7). Studies on Lacto- 

 bacillus acidophilus have shown that such thymidine compounds can 

 eventually serve as a source of material for DNA synthesis; however, 

 the rate of transfer of label is quite slow (Okazaki et al., 1959). Experi- 

 ments of this type are extremely valuable in distinguishing whether a 

 compound found in a cell is, in fact, serving as an immediate precursor 

 for DNA synthesis. 



Feinendigen et al. (1961) have obtained a similar result to that of 

 Okazaki by studying the rate of incorporation of cytidine and of 

 thymidine into DNA of animal cells. They used autoradiographic 

 techniques and demonstrated that cytidine entered a pool from which 

 it could be withdrawn over a long period for use in DNA synthesis. 

 This pool could not be affected by exogenously supplied material. In 

 contrast, thymidine entered DNA via a much smaller pool, susceptible 

 to changes in the outside medium. 



With the exception of the lily anther system and developing am- 

 phibian or echinoderm embryos, the majority of data strongly support 

 a picture in which deoxynucleoside or deoxynucleotide precursors are 

 supplied for DNA synthesis upon demand, neither accumulating to any 

 great extent before synthesis nor diminishing greatly during synthesis. 

 This conclusion is supported by autoradiographic experiments which 

 have demonstrated that the pool which can dilute exogenous thymidine 

 or deoxycytidine during incorporation into DNA is extremely small 

 (Painter et al, 1960; Taylor, 1960b). 



Little is known about the control of DNA synthesis resulting from 

 the conversion or lack of conversion of ribotides to deoxyribotides. 

 However, in vitro studies have indicated that a singular type of feed- 

 back inhibition mechanism may exist (Reichard, 1960; Reichard et al., 

 1961). Purine or pyrimidine deoxyriboside triphosphates have been found 

 to inhibit the in vitro enzymatic conversion of nucleotide monophos- 

 phates to deoxynucleotide phosphates. IMoreover, this inhibition is not 

 specific for the particular type of purine involved, i.e., deoxyadenosine 

 triphosphate will inhibit the conversion of cytidylic acid to deoxycytidine 

 monophosphate. Recent studies have shown that this system may be 

 operative in vivo as well as in vitro. Several workers have found that 

 high concentrations of deoxynucleosides in the medium will inliibit the 



