IV. CELLULAR CONTROL OF DNA BIOSYNTHESIS 171 



nhility to rleinonstrate active enzyme in extracts of a tissue does not 

 mean that the same enzyme is necessarily active in vivo. On the other 

 hand, the absence of a necessaiy enzyme may indicate a negative type 

 of control over DNA synthesis (pi'ovided the extraction procedure 

 would preserve the enzyme activity). 



The isolation and identification of the enzymes invoh'cd in the 

 production of DNA precursors have been carried out using a wide 

 variety of biological sources (see Chapter I). As was pointed out for 

 the case of bacteriophage, it has been possible to demonstrate the de novo 

 synthesis of various enzymes necessary for the production of specific 

 types of DNA. 



Few attempts have been made, however, to correlate pertinent altera- 

 tions in intracellular enzyme patterns with the DNA cycle. We have 

 already noted the induction of phosphorylating enzymes in the micro- 

 spores of the lily anther (Hotta and Stern, 1961b). The time sequence 

 was such that it was suggested that activity had been induced by the 

 deoxyriboside substrates. A more detailed study has been made of a 

 similar situation in regenerating liver. 



The liver of adult rats contains all of the enzymes necessary to 

 convert deoxy adenylic acid, deoxycytidylic acid or deoxyguanylic acid 

 to the corresponding triphosphates (Hecht et ciL, 1954; Hecht and 

 Potter, 1956; Canellakis et al, 1959; Gray et al, 1960). However, 

 enzymes necessary to accomplish the phosphorylation of thymidine are 

 lacking (Bollum and Potter, 1959; Canellakis and JNlontsavinos, 1958; 

 Canellakis et a?., 1959; Gray et al, 1960; Hiatt and Bojarski. 1960). 

 The latter appear to be present in newborn animals and are lost as the 

 animals grow older (Hiatt and Bojarski. 1960). As a result, liver slices, 

 as well as extracts of liver from normal adult animals, cannot synthesize 

 DNA in vitro. 



Following partial hepatectomy the necessary thymidylic kinases can 

 be isolated from the regenerating liver (Bollum and Potter, 1959; Canel- 

 lakis et al, 1959; Gray et a/., 1960; Hiatt and Bojorski, 1960; Bianchi 

 et al. 1961) at the time at which DNA synthesis commences. 



It is natural to assume that it is the production of these enzj^mes 

 and the consequent production of the required thymidine triphosphates 

 that leads to resumption of DNA synthesis. In examining the question 

 of the control of DNA biosynthesis, however, several questions arise: 



a. Does control lie in the production of a single enzyme or of a 

 sequence of enzymes? Recent evidence indicates that the enzymes for 

 thymidine production may not be produced until regeneration com- 

 mences (Hiatt and Bojarski, 1960). Moreover, a careful examination of 

 the time of appearance of thymidine, thymidine monophosphate, and 



