Maintenance of the A Prophage

The A oR region

The right operator region of A is the site of interplay of two regulatory factors, the cl and Cro proteins. In addition, it includes two divergent promoters with


Figure 2 Regulation of A cl and early lytic transcription. Transcription of early A genes is initiated at pL and pR, and is subject to repression by cl repressor acting at oL and oR, respectively. Transcription of cl can be initiated either at pRM or pRE. Transcripts are indicated by dashed lines. The expanded diagrams illustrate spatial relationships between pL and three repressor binding sites in oL, and among pRM, pR and three repressor-binding sites in oR. Cro protein also binds at oR and oL to reduce transcription from pR, pRM and pL. (Reproduced with permission, Cold Spring Harbor Laboratories.)

antagonistic functions, pR and pRM. The pR promoter is repressed in a lysogen, is fully active early in the lytic response, and then is dampened later during lytic development. The pRM promoter is active in a lysogen and is repressed in the lytic pathway. In vitro studies show that the two promoters interfere with each other. The cl and Cro proteins determine which promoter is recognized productively by RNA polymerase.

Despite the complexity of the regulatory network at oR, the mechanism of oR control is understood in some detail (Fig. 2). There are three 17 bp repeated sequences in oR to which cl repressor binds. The repeats have dyad symmetry and recognize a repressor dimer. Each subunit of dimer binds one half-site.

The repeats are not identical, and have different affinities for cl protein in vitro. The oRl sequence has the highest affinity, and is filled at the lowest cl concentrations. Although the oR2 and oR3 elements have equal 'intrinsic' affinities for cl, cl bound at oRl interacts cooperatively with cl bound at oR2. Thus oR2 binds cl before oR3.

Cooperativity between cl dimers has another important consequence. It causes small decreases in cl concentration to have a major effect on repression. Unlike the lac operon, therefore, the induction of which is linear with respect to inducer concentration, induction of A prophage is rapid and complete.

When cl is bound at oRl and oR2, RNA polymerase is occluded from binding to pR. At the same time, the activity of pRM is enhanced. In part,


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