Switch genetic

Repressor and Cro proteins operate a procaryotic genetic switch region... 

Ptashne, M. A Genetic Switch Gene Control And Phage Lambda. Palo Alto Blackwell, 1986. 

The Genetic Switch of Bacteriophage Lambda ( ) Provides a Paradigm for Protein-DNA Interactions in Eukaryotic Cells... 

Ptashne M A Genetic Switch, 2nd ed. Cell Press and Blackwell Scientific Publications, 1992. 

Ruezinsky, D., Beckmann, H., and Kadesch, T. (1991). Modulation of the IgH enhancer s cell type specificity through a genetic switch. Genes Dev. 5 29-37. 

Ptashne, M. (1992). A Genetic Switch, 2 Edition (Cambridge, Mass. Blackwell Scientific Publications). 

The temperate virus does not exist in its mature, infectious state inside the cell, but rather in a latent form, called the provirus or prophage state. In considering virulent viruses we learned that the DNA of the virulent virus contains information for the synthesis of a number of enzymes and other proteins essential to virus reproduction. The prophage of the temperate virus carries similar information, but in the lysogenic cell this information remains dormant because the expression of the virus genes is blocked through the action of a specific repressor coded for by the virus. As a result of a genetic switch, the repressor is inactivated, virus reproduction occurs, the cell lyses, and virus particles are released. 

The key to the genetic switch lies in the close proximity of the regulator genes for repressor and cro protein. These two genes are transcribed in opposite directions, beginning at different start points. 

Figure 5.25 Two back-to-back promoters in the region of cl and cro control the genetic switch. When cl is present, it activates its own synthesis and blocks transcription of cro. When cl is inactivated, transcription of cro can occur, resulting in the lytic cycle. The cl (repressor) protein combines with the operator, 0 .

The lambda system provides one of the best studied examples of a genetic switch, in which one or the other of two competing genetic functions occurs. Which of the two genetic functions gets the upper hand will depend initially on chance events, but once one of the two functions has become established, it prevents the action of the other function. Only under unusual circumstances, such as when induction occurs, would the dominant genetic function be superseded. 

Many reported biotransformations are initially only demonstrated on a very small scale, the substrates or products may be subject to competing reactions if other enzymes are present (this can be a serious issue in whole-cell biocatalysis), or the desired enzyme is insufficiently active or produced in low levels. For many biotransformations a little care and attention is needed in the growth of the microbe to achieve the desired results. Production of a specific enzyme from a microbe can often be increased by growing the cells in the presence of a very small concentration (typically micromolar) of an inducer. The inducer could be a natural enzyme substrate, a substrate mimic or a molecule which is in some way associated with a substrate s availability or role in metabolism. This process is called induction and represents a genetic switch which cells use to respond... 

M. Ptashne A Genetic Switch 2nd ed. Blackwell Science Cell Press Cambridge, 1992. 

Can single-molecule studies help medicine I believe the answer is yes. For example, the single-molecule question regarding genetic switches as discussed above is pertinent to research on tuberculosis, a deadly bacterial disease that kills two million people each year. There is a general phenomenon in bacteria a small population of abnormal cells, called persisters, is drug resistant. 

Fig. 28.1. In a genetic switch, the total state of the system depends on two variables whether the DNA site is occupied or not and the number of copies of the transcription factor. In the left panel, the logarithm of the steady state probability for the occupancy state and protein number is plotted. This probability acts like an effective potential. In the right panel, the effective potential for a charge transfer or two site polaron is plotted as a function of the enviromnent polarization for the two electronic states. The governing time-dependent eqnations for the two problems share many similarities...

This chapter is organized as follows for each bifurcation, we start with a simple prototypical example, and then graduate to more challenging examples, either briefly or in separate sections. Models of genetic switches, chemical oscillators, driven pendula and Josephson junctions are used to illustrate the theory. 

K. Lai, M.J. Robertson, D.V. Schaffer, The sonic hedgehog signaling system as a bistable genetic switch, Biophys. J. 

From M. Ptashne, A Genetic Switch Gene Control and Phage 1 (Cambridge, Mass. Cell Press BSI, 1986). 

Jones, B.W., Fetter, R.D., Tear, G. and Goodman, C.S. (1995) glial cells missing a genetic switch that controls glial versus neuronal fate. Cell 82 1013-1023. 

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