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Global Regulator Mechanisms

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Global Regulator Mechanisms

 Organisms control a large number of genes to respond to changes in their environment.

E. coli 

Catabolite repression 300 genes, Aerobic respiration 50 genes

 Such control mechanisms containing

one or more regulators are called

global control systems.

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1. Catabolite Repression

• Lactose genes do not work in the

presence of glucose, glucose is used first.

• It prevents the synthesis of glucose Glucose  cAMP (Cyclic adenosine monophosphate).

• cAMP is synthesized from ATP with

the enzyme adenylate cyclase.

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 Lactose genes work when glucose diminish

 cAMP synthesis is increased.

 cAMP binds to CAP (catabolic

activator protein) and affects RNA polymerase

1. Catabolite Repression

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• Bacterial cells regulate gene expression against sudden increases or decreases of nutrients in the environment.

• Bacteria that are transferred from the medium where the amino acids are excess to medium, stop the synthesis of rRNA and tRNA.

• In this way, protein synthesis in the cell stops temporarily. The growth rate of the cell, which has to perform biosynthesis of new amino acids, decreases.

2. Stringent Response

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• Two modified nucleotides (Guanosine tetrafosphate ppGpp and Guanosine pentaphosphate pppGpp) trigger.

These nucleotides, also called alarmons in E. coli, accumulate rapidly in the cell in the absence of amino acids.

• Alarmones are synthesized by a special protein called RelA. RelA uses ATP as phosphate donor.

• In the absence of amino acids, an uncharged tRNA without amino acid binds to the ribosome and the ribosome activity stops.

• During this event, RelA, activated by a signal from the ribosome, binds to the 50S subunit of the ribosome and alarmons are synthesized.

2. Stringent Response

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• Alarmons inhibit the transcription of rRNA and tRNA genes in the cell by acting on RNA polymerase.

• They also activate related genes for the biosynthesis of missing amino acids.

• They stop operons that encode enough amino acids.

• DNA synthesis and inhibition of division in the cell are among the secondary effects of this control mechanism.

2. Stringent Response

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Most of the global control systems are controlled by alternative sigma factors (the subunit of the RNA polymerase enzyme recognizing the promoter region).

Bacteria have a different number of sigma factors. In E coli, 7 sigma factors (σ70, σ54, σ38, σ32, σ28,

σ24, σ19, each representing different genes) are identified in kilodaltons.

E coli σ32 (RpoH) lyses in the cell immediately after synthesis. If the cell encounters a significant

increase in temperature, this heat shock prevents the destruction of σ32.

As a result, the amount of this sigma factor in the cell increases. RpoH (σ32) enhances transcription of genes encoding heat shock proteins. These proteins are produced in the cell during the heat shock

response.

3. Heat Shock Response

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Three major classes of heat shock proteins (Hsp70, Hsp60 and Hsp10) were determined in E coli.

The Hsp70 protein is the DnaK protein, which

prevents aggregation of newly synthesized proteins and makes the unfolded proteins stable.

At normal temperatures, DnaK binds to RpoH. At high temperatures, DnaK is separated from RpoH and binds to proteins that cannot be folded at this temperature.

The amount of RpoH in the cell increases, resulting in heat shock genes being transcribed. When the temperature drops, DnaK rapidly inactivates RpoH, resulting in reduced synthesis of heat shock

proteins.

3. Heat Shock Response

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Regulation of Growth in Model Bacteria

 Differentiation is characteristic of multicellular organisms.

 Only a portion of prokaryotic single cell microorganisms (eg Bacillus spp. And Caulobacter spp.) Form two

different cell types in their growth.

 In order to achieve such a differentiation, at least three important steps must be performed.

 1. Starting the response,

 2. Formation of two different cells

 3. Communication between these cells

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Bacillus Sporulation

 Adverse environmental conditions allow some sporulation proteins, called sporulation factors, to be activated by phosphating.

When one of these proteins, SpoOA, is phosphorylated, sporulation starts.

Phosphorylated SpoOA protein removes phosphate from the SpoIIA protein.

The figure shows that sporulation starts with the separation of phosphate from the SpoIIA sporulation factor.

 In this way, the development of the endospore is controlled by four different sigma factors.

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Caulobacter Differentiation

 An undivided moving cell

 A second cell with immobilized stem that can proliferate

 The three regulatory proteins (GcrA, CtrA and DnaA) achieve this differentiation.

 First, CtrA is activated by phosphating with external signals.

 This activates the genes necessary for

flagella synthesis and cell formation.

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D. RNA regulation

1.Antisens RNA: translation-level control

 RNA is used instead of a protein  Occurs in prokaryotic and eukaryotic cells  40 - 400 small RNAs (sRNAs) that do not encode proteins are used.

2.Riboswitches

3.Attenuation

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