Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four mutants of Escherichia coli KL16 resistant to the antibiotic Thiolutin have been isolated. This drug was earlier reported to be an inhibitor of RNA chain elongation. The first mutant, TLrI, is resistant only in rich or partially rich media: it can, however, grow in minimal medium containing the drug with a very long doubling time. The other mutants TLrII, TLrIIIa and TLrIIIb are resistant in rich as well as minimal media. beta-galactosidase could not be induced in TLrI and TLrII in the presence of thiolutin whereas the enzyme is constitutively synthesised in TLrIIIa and TLrIIIb irrespective of the drug. The mutants do not support the development of phage T4 in presence of the drug, if the drug is added along with the phage, but "escape" the inhibition if phage development is allowed to proceed for some time before the addition of the drug. The time of this escape is characteristic of the mutant. Even in a sensitive strain, T7 growth escapes inhibition very soon after infection, around the time the phage-specific RNA polymerase is synthesized. In the parent strain the kinetics of inhibition of beta-galactosidase induction resembles more the inhibition caused by rifampicin than by streptolydigin. It is proposed that thiolutin could be an inhibitor of RNA chain initiation and resistance might be due to mutation in the subunit(s)/factor(s) involved in initiation.
Mol Gen Genet 1976 Apr 23
PMID:Thiolutin resistant mutants of Escherichia coli are they RNA chain initiation mutants? 77 14

By using rifampicin to increase the rate of beta and beta' synthesis in a heterodiploid strain of E. coli carrying the mutation rifpr (Km7), which codes for a rifampicin sensitive RNA polymerase to which the drug binds weakly, and the dominant mutation rifRD, which codes for a rifampicin resistant RNA polymerase, the concentration of these subunits in the cell was increased 1.6 fold. Measurements made after removal of rifampicin from the cells showed that the excess beta and beta' subunits did not reduce the rate of their own synthesis below normal.
Mol Gen Genet 1976 May 07
PMID:Evidence against autorepression of the betabeta' operon in Escherichia coli. 77 88

During the course of kinetic studies on the synthesis of RNA polymerase subunits in Escherichia coli K12, strain Km7 (CP372), certain anomalies were found that seemed to be associated with the system of reversible inhibition of RNA and protein synthesis by rifampicin. To find a possible explanation for these anomalies, effects of rifampicin on RNA chain elongation and on residual synthesis of polymerase subunits were investigated with several strains including Km7. Examination of mRNA synthesis for the tryptophan operon suggested that RNA chain growth as well as RNA chain initiation is inhibited at high drug concentration (500 mug/ml), wheras RNA chain initiation is inhibited specifically at low concentration (20 mug/ml). Analysis of effect of rifampicin concentration on total RNA synthesis gave results that are also consistent with this conclusion. These results emphasize the need for selecting a proper drug concentration whenever rifampicin or other related antibiotic is used as a specific inhibitor of transcription initiation. When rifampicin was added to a culture of these strains absolute rates of synthesis of all subunits of RNA polymerase increased for several minutes and then decreased. The extent of this transient stimulation varied depending on the strain, drug concentration and other conditions, but was most striking for the beta and sigma subunits with strain Km7 at high drug concentration (500 mug/ml). With a rifampicin-sensitive wild-type strain tested, the maximum stimulation was found at about 50 mug/ml of the drug, with a particularly marked effect for sigma subunit. Streptolydigin, on the other hand, inhibited the synthesis of core subunits much faster than the bulk of protein, but inhibited synthesis of sigma subunit only after a lag. Hence a specific effect of rifampicin but not the inactivation of beta subunit per se appears to be involved in transient stimulation of polymerase synthesis observed. Implications of these findings on the control of RNA polymerase synthesis are discussed.
Mol Gen Genet 1976 Jun 15
PMID:Effects of rifampicin on synthesis and functional activity of DNA-dependent RNA polymerase in Escherichia coli. 78 14

The analysis of tryptic peptides was performed on the unassembled as well as assembled form f alpha subunit of the DNA-dependent RNA polymerase from Escherichia coli. The peptide profiles obtained by Dowex 50 column chromatography of the unassembled alpha subunit prepared from cells, either pulse-labeled or continuously labeled with radioactive lysine or arginine, were essentially identical with those of the alpha subunit from intact RNA polymerase. The results suggest that newly synthesized free alpha subunit is assembled into the polymerase structure without any remarkable modifications. The number of lysine- and arginine-containing peaks were close to the values expected from the amino acid composition of alpha subunit assuming that the two alpha subunits in RNA polymerase core enzyme have identical primary structure.
Mol Gen Genet 1976 Jun 15
PMID:Peptide analysis of RNA polymerase alpha subunit from Escherichia coli: comparison of free with assembled form. 78 18

The influence of mutations in structural genes of beta and beta subunits of RNA polymerase upon the synthesis of these subunits in E. coli cells have been investigated. An amber-mutation ts22 in the beta subunit gene decreases the intracellular concentration of this subunit and the rate of its synthesis. At the same time the concentration and the rate of beta subunit synthesis is increased. These suggest the compensatory activation of the RNA polymerase operon that takes place under the conditions of shortage of one of the subunits. Reversions as well as more effective suppression of ts22 amber mutation, achieved by streptomycin addition, substitution of su2 by sul, or by specific mutations, result in a rise of beta and drop of beta subunit concentration and synthesis in ts22 mutant. TsX missense-mutation in the beta subunit gene alters the properties of the enzyme increasing, at the same time, the concentration and the rate of synthesis of both beta and beta subunits, particularly at a nonpermissive temperature. This points to an inversely proportional relationship between the rate of synthesis of RNA polymerase subunits and the total intracellular activity of the enzyme. Extra subunits are rapidly degraded in ts22 and tsX mutants. The whole complex of our data and those of others suggest that the regulation of the synthesis of RNA polymerase subunits is accomplished by interaction of a negative and a positive mechanisms of regulation which include not only activators and repressors but the enzyme itself as well.
Mol Gen Genet 1976 Jun 15
PMID:The influence of mutations upon the synthesis of RNA polymerase subunits in Escherichia coli cells. 78 19

In a rifS/rifR heterodiploid strain of E. coli, a 4 minute pulse of rifampicin can induce a prolonged (greater than 60 min) increase in the rate of synthesis of the RNA polymerase subunits, beta and beta'. The application of a constraint on the fidelity of protein synthesis during, but not after, the rifampicin pulse partially arrests the development of this capacity for subunit synthesis. I discuss the implications of these findings in relation to the control of the BB' operon in E. coli.
Mol Gen Genet 1976 Jul 05
PMID:Rifampicin-induced protein synthesis: A pre-requisite for increased expression of the beta beta' operon in Escherichia coli. 78 12

Bacteria with specific temperature sensitive lethal mutations in the gene for the beta' subunit of RNA polymerase synthesize both the beta and beta' subunits at a several fold higher rate at 42 degrees C than wild-type cells relative to total protein. Synthesis of the alpha and sigma subunits proceeds at essentially the wild-type rates under these conditions. In contrast, a mutant with a temperature sensitive lethal mutation in the beta subunit gene synthesizes beta and beta' at 42 degrees C at slightly lower rates than wild-type, while alpha and sigma synthesis is not significantly altered. In all of the mutants at 42 degrees C, newly synthesized alpha subunits are stable, while the beta, beta' and sigma subunits are rapidly degraded. The apparent uncoupling of betabeta' and alpha subunit synthesis seen in the beta' mutants at 42 degrees C might suggest that the synthesis of these subunits is at least in part controlled by different mechanisms.
Mol Gen Genet 1976 Aug 19
PMID:Altered synthesis and stability of RNA polymerase holoenzyme subunits in mutants of Escherichia coli with mutations in the beta or beta' subunit genes. 78 54

ppGpp alters the initiation specificity of RNA polymerase holoenzyme in vitro in a direction which mimics the stringent response in vivo. The transition temperature for opening rRNA promoters is increased by the nucleotide, that for opening phi80 promoters is unaffected. This implies that RNA polymerase can discriminate between different types of promoter. ppGpp may act by effecting a structural change in the enzyme.
Mol Gen Genet 1976 Aug 19
PMID:Modulation of RNA polymerase specificity by ppGpp. 78 60

RNA polymerase from T4 infected cells supplemented with E. coli sigma polypeptide has a lower affinity for rRNA promoters than RNA polymerase from uninfected cells. The pattern of transcription by the phage modified polymerase is qualitatively similar to that of the vegetative polymerase in the presence of ppGpp. We suggest that E. coli polymerase holoenzyme normally exists in at least two conformational states, one with a high affinity for rRNA promoters and another with a low affinity, and that T4 infection stabilises the low affinity form.
Mol Gen Genet 1976 Sep 23
PMID:Phage T4 infection restricts rRNA synthesis by E. coli RNA polymerase. 78 64

RNA polymerase isolated from ts XH56, a conditional lethal mutant unable to grow and synthesize RNA at 42 degrees, was found to be temperature sensitive in vitro. The mutation affects the beta' subunit as determined by mixed reconstitution of isolated subunits from wild-type and mutant enzyme. The mutant RNA polymerase is unstable; addition of glycerol stabilizes the enzyme and increases its activity on native DNA. In addition, the mutant enzymes is sensitive to high ionic strength. Both high temperature and high ionic strength do not affect chain elongation; thus, the mutation renders the enzyme unable either to bind to or melt out promotor sites. From these data we conclude that the beta' subunit plays an important role in promotor selection.
Mol Gen Genet 1976 Sep 23
PMID:Characterization of a ts beta' mutant RNA polymerase of Escherichia coli. 78 68


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