100 



S. S. COHEN 



The first indication of an unusual role of the nucleus in nucleic acid 

 metabolism stems from the work of Marshak (1941), who showed that when 

 P^2 is injected into an animal, the rate of uptake by the nucleus is far more 

 rapid than that by cytoplasm. He showed that the rate of P^^ uptake in nuclei 

 was sufficient to accomit for the doubling of nuclear P in one division time, 

 and that, in a lymphoma nucleus of division time 27 hours, this amounted 

 to 2.8 X 10^ nucleic acid nucleotides per second. 



In subsequent studies, it was demonstrated that when an animal was 

 administered glycine-N^^ (Bergstrand et al., 1948), P^^ (Marshak, 1948), or 

 the pyrimidine orotic acid-C^* (Potter et al., 1951), the early isotope content 

 of nuclear RNA in liver was far greater than that of any cytoplasmic fraction. 

 A typical experiment of this type is given in Fig. 15. It can be seen that the 



O 10 20 30 40 50 60 96 



Time after administration of P-^^(hr) 



Fig. 15. Relative specific activities of the cytidylic acids of nuclear RNA, mito- 

 chondrial RNA, and microsomal RNA separated from rabbit liver at various times 

 after the administration of P^^. The points for mitochondrial and microsomal RNA were 

 coincident and the resultant curve has been termed "granules." (Smellie, 1955.) 



activity of a nucleotide (cytidylic acid) of nuclear RNA rose to a maximum 

 rather early and fell precipitously, while the same moiety in cytoplasmic 

 RNA reached a maximum somewhat later and fell more slowly. The activity 

 of this substance in cell sap was shghtly greater than that of various granules, 

 which in tliis experiment had comparable activities. As summarized by 

 Smellie (1955), many workers have confirmed these results, although a few 

 have considered that one or the other of the cytoplasmic particles had 

 slightly greater rates of incorporation than the other. 

 In any case, the nucleus is evidently an important site of RNA s5rQthesis, 



