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23 lac Repressor

Jay D. Gralla


Physiological repression of the lac operon involves a DNA loop stabilized by the interaction of two pairs of DNA-recognition domains with two separated DNA sequence elements. The critical roles of DNA sequences, repressor protein domains, and the competition between RNA polymerase and repressor are discussed in this review.

“The reports of my death are greatly exaggerated,” said Mark Twain, and so has it been with study of the lac operon. The 1990s mark the sixth decade in which lac has been studied as a genetic system (Monod and Audureau 1946), and such work continues to serve both as a model for comparison and as an engine for change. Although some interest in the lac operon is mere idle curiosity about the way that blue colonies appear, much more is centered on how lac repressor binds simultaneously to two remote operators and what it does there in cooperation with RNA polymerase to accomplish regulation.

Over the years, the lac system has been a proving ground for testing new concepts and developing new techniques. The intensity of investigation is staggering; thousands of point mutations have been introduced into the protein (see Kleina and Miller 1990 and references therein) and bases in the operator have not only been mutated extensively (see Lehming et al. 1990 and references therein), but have even been changed to specifically modified nucleotides to test groups involved in recognition (see Goeddel et al. 1978). Such essential techniques as footprinting, chemical probing, gel shift analysis, and blue colony...

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