Nuclear control of enzymatic activities 



by 



JEAN BRACHET 



Laboratoire de Morphologie animale, Universite libre de Bruxelles 



INTRODUCTION 



While the importance of the cell nucleus in heredity is a well-established fact, its 

 general significance for the life of the cell still remains mysterious. Since the famous 

 experiments on merotomy in Protozoa by Verworn (1881), Balbiani (1889) and 

 their successors (for recent contributions to the problem, see Weisz (1948) and 

 Tartar (1953)), it has been known that an enucleate piece of an unicellular organism 

 is usually unable to regenerate; however, the important experiments of Hammerling 

 (1934) on the giant unicellular alga Acetabularia have clearly shown that, provided 

 light is supplied, a non-nucleated fragment is capable not only of growth but even 

 of real morphogenesis. 



Three main hypotheses have been put forward to account for these experimental 

 facts: (1) the nucleus is the main centre of cellular respiration (Loeb, 1899); (2) the 

 nucleus is a storehouse of enzymes or of substances which can activate enzymes 

 (E. B. Wilson, 1925) ; (3) the nucleus is the main centre of protein synthesis (Caspers- 

 son, 1941). These three theories will be discussed critically on the basis of experi- 

 ments performed in this laboratory on unicellular organisms [Amoeba proteus and the 

 alga Acetabularia mediterraned). 



However, a few words should be said first about the results obtained by the many 

 biochemists who have been working on homogenates : it is known, from the experi- 

 ments of Claude (1943), that it is possible to isolate, by progressive centrifugation of 

 extracts of crushed cells, various fractions which respectively consist of nuclei, 

 mitochondria and microsomes (small granules). It is now a well-established fact that 

 the mitochondria contain the vast majority of the oxidative enzymes and that they 

 can oxidize both carbohydrates and fatty acids completely; furthermore, if they are 

 supplemented with the necessary soluble coenzymes, they are even able to couple 

 these oxidations with phosphorylations, i.e. to synthesize the energy-rich phosphate 

 bonds characteristic of adenosinetriphosphoric acid (ATP). 



The role of the microsomes has long been more mysterious; as they contain a large 

 proportion of ribonucleic acid (RNA) and as this substance seems to play a part in 

 protein synthesis (Brachet, 1941; Caspersson, 1941) it has been suggested that the 

 microsomes are important agents in protein synthesis (Brachet and Jeener, 1944; 

 Brachet, 1945). Such a suggestion has recently found very strong support in experi- 

 ments on the incorporation of labelled amino-acids into proteins by various cell 

 fractions (Hultin, 1950 a,b; Stern and Mirsky, 1952 ; Siekewitz, 1952 ; Gale and Folkes, 

 1953, etc.) : they clearly show that microsomes are more active in protein synthesis 



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