40 CONTROL MECHANISMS IN CELLULAR PROCESSES 



Mechanism of Repression 



The Regulator Hypothesis. The diversity and abundance of re- 

 cent contributions— both l^iochemical and genetic— to the field of 

 repression make it attractive as well as difficult to attempt some kind 

 of integration of the results in the context of molecular mechanisms. 

 As a point of departure, it may be helpful to consider a hypothesis 

 of repression that was formulated in general terms in 1956, on the 

 occasion of the Symposium on the Chemical Basis of Heredity at the 

 McCollum-Pratt Institute (Vogel, 1957a). 



It seemed reasonable to assume that repression of enzyme forma- 

 tion reflects an interference with the functioning of the enzyme- 

 forming system. The hypothesis addressed itself to the question of 

 how a repressor of low molecular weight compared to that of a pro- 

 tein can hamper the performance of an enzyme-forming system. It 

 was proposed that this type of interference involved the binding of 

 a newly synthesized enzyme molecule to the site of its formation 

 through the agency of the repressor (or its "active" derivative). 

 Such binding might block the further production of enzyme mole- 

 cules until the enzyme-forming site is freed again. Whether this 

 kind of binding would involve the catalytically active site of the 

 enzyme or some other site is a question that was explicitly left open. 

 It was pointed out that induction can also be viewed in terms of 

 removal of an enzyme molecule from its site of synthesis (Vogel, 

 1957a). If repression reflects a binding of nascent protein to its site 

 of formation, induction could reflect the neutralization of such a 

 binding effect, and the possibility of an antagonism of inducers and 

 repressors (collectively called regulators) of one and the same en- 

 zyme was subsequently considered; a unified hypothesis, termed 

 regulator hypothesis, was thus proposed (Vogel, 1957b). It was 

 also contemplated that, at least in some instances, induction could 

 comprise a ("simple") promotion of the removal of an enzyme 

 molecule from its site of synthesis (Vogel, 1957a, 1957b). Such a 

 promotion effect, which would not involve an antagonism to a re- 

 pressor, might be thought of as "positive induction." Cogent evi- 

 dence in favor of a repressor-inducer antagonism has come from the 

 work of Pardee et al. (1959), described in the preceding section. 

 While it seems likely that this kind of mechanism is widespread in 

 similar systems, the possibility of positive induction in some cases 

 should perhaps be kept in mind. 



