Regulatory gene defects

A mutant defective in the chemotaxis toward 4-hydroxybenzoate in P. putida was obtained by Tn5 transposon mutagenesis, and allowed identification of a gene cluster pcaRKF that encodes enzymes of the 3,4-dihydroxybenzoate branch of the (i-ketoadi pate pathway pcaR encodes regulatory genes, pcaK the thiolase in the last step of the pathway, and pcaF is involved in transport of, and chemotaxis toward 4-hydroxybenzoate (Harwood et al. 1994). 

The discovery of X-linked agammaglobulinaemia in 1952 was only a prelude to the discovery of a large number of deficiency states in the immunological systems. At present, almost all the well-defined immunodeficiencies in man and animals have a genetic basis. Despite this fact, it is curious that very few examples of structural gene defects have come to light. Most of the immunodeficiency diseases appear to result from the failure of some regulatory process, and a disproportionate number of them are X linked. 

Mutations in the regulatory genes usually produce dramatic results. A mutant repressor gene may produce a defective protein which cannot bind to the operator and would result in continued protein synthesis. Enzymes which, in normal cells, are inducible thus become constitutive. Constitutive operator mutants also occur where an altered base sequence in the DNA of the operator region results in loss of the ability to bind the normal repressor protein. 

A number of abnormalities of protein synthesis are known in terms of defects of the structural gene. Specific abnormalities of the regulatory genes in mammalian cells have not been demonstrated. One can only speculate at this time about the consequences of defects in the promoter and operator. 

Defects in the regulatory gene may be any of those that occur for the structural gene so that the amount of repressor synthesized may vary or the structure of the repressor may be altered so that its function is abnormal. 

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