Why does lambda possess regulation systems as complicated as those described above? Part of the answer is that lambda must switch between two states, lytic and lysogenic. Even so, this does not explain why a simple repressor like that found in the lac operon could not suffice for lambda’s needs. In part the answer lies in the fact that lambda must regulate its gene activities over a much greater range than lac. The basal level of the lac operon is 0.1% of the fully induced level, and there is no apparent reason why a lower basal level would serve any useful purpose. A similar basal level of repression of lambda early genes would be disastrous, for lambda would then have a high rate of spontaneous induction from the lysogenic state. Experimentally the spontaneous induction rate is low. Typically in a doubling time, fewer than one cell out of 106 spontaneously cures of lambda or induces. This low rate means that the basal level of expression of the lambda early genes is very low indeed.

Suppose the basal level of expression of a repressible operon similar to the lac operon is to be generated by increasing the concentration of repressor. To reduce the basal level to 1/1000 of normal, the repressor level would have to be raised 1000-fold. Not only would this be wasteful of repressor, but even worse are the implications for induction. With 10,000 molecules of repressor per cell, inducing the early genes to greater than 50% of maximal would require inactivating approximately of 9,998 repressor molecules per cell. Although lambda phage may like to hitch a free ride in healthy cells, once viability of the cells is in question because of damage to the host DNA, lambda bails out and induces. The lambda in very few cells indeed would be capable of inducing if 99.995% of the repressor within a cell had to be inactivated before early genes could be turned on efficiently.

One of lambda’s solutions to the problem of being either repressed or induced has been to evolve a nonlinear induction response. At the normal levels of repressor, of about 100 dimers per cell, lambda is fully repressed. However, if 90% of repressor has been inactivated, the p_R promoter of lambda is 50% of fully induced. For comparison, inactivation of 90% of lac repressor induces the lac operon only 3% (Table 1). The highly cooperative binding of repressor to O_R1 and O_R2 is largely responsible for lambda’s nonlinear response. This can be understood quantitatively as follows. Since the high cooperativity in repressor binding means that most often O_R1 and O_R2 are either unoccupied or simultaneously occupied, it is a good approximation to assume that two repressors bind to operator at the same time. Combining the binding equation that defines the dissociation constant with the conservation equation and solving yields the ratio of free operator O to total operator O_T, that is, the relative amount of derepression as a function of repressor concentration:

As the concentration of free repressor falls from a value a bit above KD^1/2 to a value below KD^1/2, promoter activity, which is proportional to the fraction of operator unoccupied by repressor, O/O_T, increases rapidly due to the R² term. Hence very sharp changes in operator occupancy can be produced with relatively small changes in the concentration of repressor (Fig. 1).

Table1. Derepression of the Lambda Promoter p_R and the lac Promoter as a Function of the Amount of Repressor Remaining Active

Fig1. Exaggerated example of the nonlinearity in the repression of p_R as a function of repressor concentration. The operator is fully occupied and off at concentration R1; at a repressor concentration about half of R1, the operator is unoccupied and the promoter is largely derepressed.

Lambda repressor uses another mechanism in addition to cooperative binding to the operators to increase the nonlinearity in its response to repressor concentration. Only dimers of the repressor polypeptide are able to bind to lambda operators under physiological conditions. The dissociation constant governing the repressor monomer-dimer reaction is such that a small reduction from the normal intracellular concentration of repressor sharply reduces the concentration of active repressor dimers. The combination of repressor monomer association dissociation, cooperativity in repressor binding, and the need for sustained synthesis of N protein for lambda induction and development produces a very nonlinear induction response to changes in repressor level. At one concentration of repressor, lambda is highly stable as a lysogen, but at a lower concentration, lambda almost fully derepresses p_L and p_R.

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اخبار العتبة العباسية المقدسة

قسم العلاقات العامة يختتم فعاليات محطات فتية الكفيل الثقافية في محافظة نينوى

ما الخدمات التي قدّمها موكب أشبال الطفّ لزائري عاشوراء؟

العتبة العباسية المقدسة تنظّم مسيرات عزائية لإحياء ذكرى عاشوراء في نينوى

قسم الشؤون الفكرية يحيي ذكرى استشهاد الإمام الحسين (عليه السلام) في القارة الإفريقية

المزيد

الآخبار الصحية

تناول الجبن.. مفيد للجسم أم خطر يهدد صحتك؟

طبيبة أسنان تحذر.. لا تتجاهل هذه العلامة بعد التنظيف

يجب أن تأكل المزيد من الشمام هذا الصيف.. إليك السبب ؟

تأثير صحي كبير.. كم بيضة يجب أن تتناول يوميا؟

المزيد

الآخبار التكنلوجية

أداء خلايا البيروفسكايت الشمسية تحت الماء قد يزيد كفاءة تحويل الكهرباء

مسافة الأمان: أساس القيادة الآمنة وتجنب الحوادث

هل القيادة السريعة تعني استهلاك اكثر للوقود؟

لماذا يعتبر كوكب المريخ غير صالح للحياة؟

المزيد

مواضيع ذات صلة

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

Phage Replication

Genotoxicity Through Potential Off-target Nuclease - Induced Double - Strand Breaks

A Broad Range of Genomic Changes by Homologous Recombination–Mediated Genome Editing

Early Transcription of Genes N and Cro

Lambda’s Relatives and Lambda Hybrids

The Genetic Structure of Lambda

The Physical Structure of Lambda