6 CONTROL MECHANISMS IN CELLULAR PROCESSES 



Nevertheless at present, the most fruitful approach to the analysis 

 of DNA alterations appears to be an indirect one— the genetic anal- 

 ysis of mutants which produce altered proteins ( Benzer, 1957; Yanof- 

 sky and St. Lawrence, 1960 ) . This approach should reveal whether 

 or not there is a linear correspondence between genetic sites and 

 amino acid sequence. Furthermore, from such studies it is hoped 

 that evidence can be obtained relating specific genetic damage to 

 specific modifications of an enzyme ( Suskind, 1957b ) . 



It is this approach, using the tryptophan synthetase ( Tsase ) sys- 

 tem in N. crassa and E. coli, with which this paper will be concerned. 

 The studies described have been carried out at Yale by Dr. Bonner's 

 group, at Stanford, and at Johns Hopkins. This paper, in attempting 

 to present an over-all picture of the tryptophan synthetase system, 

 has drawn on the work of many investigators in these laboratories, 

 including Drs. J. De Moss, Y. Suyama, and A. Lacy; Drs. I. Crawford, 

 P. Lerner, B. Maling, D. Helinski, M. Rachmeler, and J. Stadler; and 

 Drs. W. Mohler, M. Carsiotis, and Mrs. D. Ligon. 



Experimental 



The material we would like to discuss can best be considered in 

 several sections: ( 1) A comparison of the N. crassa and E. coli tryp- 

 tophan synthetase (Tsase) systems. Studies with these systems offer 

 a unique opportunity to correlate the properties of an enzyme cat- 

 alyzing the same reactions in two different microorganisms, with 

 mutations occurring at specific sites within well-defined genetic 

 regions. (2) Progress in studies of the effects of mutations on the 

 coli and Neurospora enzymes at the protein and amino acid level. 

 (3) Some of the intergenic and intragenic interactions affecting the 

 function of genetically damaged tryptophan synthetase. 



Three reactions are catalyzed by the wild type Tsase of Neu- 

 rospora and coli (Yanofsky, 1960). These reactions are shown in 

 Fig. 1-1.^ The physiological essential reaction appears to be reac- 

 tion 1. 



In Neurospora these three reactions are catalyzed by a single pro- 

 tein, having a molecular weight of about 140,000 ( Mohler and Sus- 

 kind, I960). In coli the enzyme system can be readily dissociated 



4 The following abbreviations are used in the text: B^al PO4 = pyridoxal phosphate; 

 Tsase = tryptophan synthetase; CRM = cross-reacti\ e material; In = indole; InGP = 

 indole glycerol phosphate; Ser = L-serine; and TP = triose phosphate. 



