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Global Control Systems

Susan Gottesman, Frederick C. Neidhardt


An efficient way to coordinate the synthesis of proteins that are required in fixed stoichiometric ratios under all environmental conditions is to place them in a single transcriptional unit. Prokaryotic cells make extensive use of this means of regulating the expression of genes that produce proteins of related function, such as those involved in the biosynthesis of histidine or of tryptophan. Most of the structural genes in species such as Escherichia coli are organized into operons consisting of two to eight individual cistrons (Bachman and Low 1980). A major portion of the work of molecular genetics in the past few decades has been devoted to unraveling the variety of ways in which the transcriptional activity of operons is adjusted by the interaction of specific protein regulators (activators and repressors), or by the process of attenuation at control sites (promoter-operator) near the beginning of each operon.

That single regulatory molecules regulating single operons is only the first step in understanding cell regulation was suggested by the long-standing observation that sugar utilization operons as a group respond to the presence of glucose in the medium (Magasanik 1962). This catabolite repression effect was demonstrated to be mediated through the cellular level of cAMP, although how the changes in cAMP are brought about is still not clear. The isolation of mutations in the cAMP synthesis (cya) and sensing (crp) systems was the first genetic approach to complex networks (Perlman and Pastan 1969; Emmer et al. 1970; Schwartz and Beckwith 1970). Two aspects of...

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