In this section we discuss how lambda escapes from the lysogenic state and enters a lytic cycle. One time at which this occurs follows host DNA damage and repair. The signal a phage uses for detection of this damage is the extensive binding of RecA protein to single-stranded DNA that accumulates at a replication site when extensive DNA damage is present. Apparently when polymerized along the single-stranded DNA, RecA is held in a shape that interacts with LexA and lambda repressor. The interaction stimulates the inherent self-cleavage activity of these repressors (Fig. 1). Once cleaved, these repressors are no longer able to repress.

Fig1. LexA protein represses its own synthesis as well as that of RecA protein. Cleavage of LexA and lambda repressor activated by RecA derepresses the lexA, recA, and lambda operons.

In a nonlysogenic cell the genes that are normally repressed by LexA protein are the lexA gene itself, the recA gene, and a set of about 20 others that are part of the SOS system. Known functions of this system are to repair damaged DNA and to postpone cell division until repair is completed. Once repair is completed, the single-stranded DNA no longer available to activate RecA. Consequently, newly synthesized LexA protein is no longer cleaved and it therefore represses synthesis of RecA and the other proteins of the SOS system. In a normal nonlysogenic cell, the SOS system switches off when it is no longer needed.

The proteolytic activity of LexA and CI which is stimulated by RecA protein disconnects the N-terminal domain of the lambda repressor from the C-terminal domain (Fig. 2). A number of physical experiments with protease-digested repressor or with N-terminal fragments of repressor produced from nonsense mutations have revealed that the N-terminal half of the protein folds up to form a compact domain that can bind to operator. The C-terminus also folds to form a compact domain, but this domain is primarily responsible for the dimerization of repressor. The C-terminal domains lacking N-terminal domain still dimerize, whereas the N-terminal fragments do not.

Fig2. Representation of the structure of lambda repressor and the effects of cleavage by RecA protease. The DNA-binding domains are shown contacting one another while on DNA because a small bit of the dimerization energy derives from such an interaction.

As required for induction, the affinity of the monomeric N-terminal domain for operator is much lower than that of the intact dimeric repressor. Furthermore, the N-terminal domains do not show strong cooperativity in their binding to adjacent operators. In the next section we will see why the proteolytic cleavage and elimination of dimeric DNA-binding domains greatly reduce the affinity of repressor for operator. As a result of this reduced affinity, repressor comes off the DNA and the phage induces.

The N-terminal domain of repressor makes protein-protein contacts with RNA polymerase when it stimulates transcription from the p_RM promoter (Fig. 3). The stimulation provided by this positive-acting factor is similar to the stimulation provided by CRP protein. The repressor accelerates the isomerization rate by RNA polymerase after it has bound to p_RM. CRP bound near position -41 on promoters also stimulates isomerization.

Fig3. The activation of RNA polymerase at p_RM by two repressor dimers bound at O_R1 and O_R2.

Two types of evidence indicate that it is the N-terminal domain of repressor that contacts RNA polymerase. The first is the existence of mutations in lambda repressor that eliminate the positive stimulation of p_RM by repressor when it occupies O_R1 and O_R2. These lie in the portion of the protein immediately adjacent to the helices of the N-terminal domain that contact operator. The second is that high levels of the N-terminal domain are capable of stimulating p_RM . 

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جمعية كشافة الكفيل: المجالس الحسينية تعلّم الفتية قيم نهضة الإمام الحسين (عليه السلام)

عَبرَ المجالس الحسينية.. المجمَع العلمي يقدّم محاضرات دينية وتلاوات قرآنية في بغداد والنجف وميسان

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مواضيع ذات صلة

Genome Editing of Immune Effector Cells for Safer and More Potent Cancer Therapies (CAR-T Cells)

Therapeutic Genome Editing for Hematologic Diseases: β-Thalassemia

Therapeutic Genome Editing for Hematologic Diseases: Sickle Cell Disease

TFIIIA Binding to the Middle of its Gene as Well as to RNA

Biology of 5S RNA Synthesis in Xenopus

Entropy, a Basis for Lambda Repressor Inactivation

The Need for and the Realization of Hair-Trigger Induction

Site for Cro Repression and CI Activation

Chronology of Becoming a Lysogen

N Protein and Antitermination of Early Gene Transcription

Spontaneous Mutations in bacteria

Mechanisms of Gene Transfer in Bacteria