Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Similar to its inhibitory effect on mammalian DNA topoisomerase II, the cytotoxic drug VM26 (teniposide) also interferes with the breakage-reunion reaction of Drosophila melanogaster DNA topoisomerase II. VM26 induces topoisomerase II-mediated DNA breakage in vitro and in cultured D. melanogaster cells presumably by stabilizing an enzyme-DNA cleavable complex. The drug-induced DNA breaks on D. melanogaster hsp70 genes were mapped in cultured cells using the indirect end-labeling procedure. Multiple and specific cleavage sites occurred at both the 3' and 5' ends of the hsp70 genes. A number of these cellular topoisomerase II cleavage sites mapped close to the DNase I-hypersensitive regions of the hsp70 genes. The intensities of several topoisomerase II cleavage sites changed significantly on heat shock induction. Treatment of cultured D. melanogaster cells with VM26 at 25 degrees C resulted in the stimulation of transcription of the hsp70 genes. These results suggest that inhibition of DNA topoisomerase II may lead to heat shock transcription.
Mol Cell Biol 1986 Apr
PMID:In vivo localization of DNA topoisomerase II cleavage sites on Drosophila heat shock chromatin. 302 86

The binding of a ligand to a one-dimensional lattice in the presence of a second ("rider") ligand, which binds only to the first ligand (piggy-back binding), is studied. A model derived from this study is used to analyze the effects of co-operativity on the reaction rates of enzymes activated by polymeric cofactors that provide multiple binding sites for the enzyme. It is found that in the presence of strong co-operativity, the steady-state reaction rates of polymer-activated enzymes can be very different from the Michaelis-Menten paradigm. By adjusting the co-operativity parameters and the binding constants of the ligands, the model can generate apparent auto-catalytic enhancement by substrates at low substrate concentrations and apparent substrate inhibition at high substrate concentrations. The model is shown to be able to explain the differences in the rates of ATP hydrolysis by DNA gyrase in the presence of long versus short DNA molecules and in the presence of long DNA molecules at different gyrase to DNA ratios.
J Mol Biol 1986 Jul 20
PMID:Co-operativity and enzymatic activity in polymer-activated enzymes. A one-dimensional piggy-back binding model and its application to the DNA-dependent ATPase of DNA gyrase. 302 51

The study deals with Mu growth in cells carrying a temperature-sensitive mutation in the gene of DNA gyrase B subunit. At a nonpermissive temperature the Mu growth is shown to be blocked in the host gyrB ts mutant both on infection and on prophage induction. Mu DNA does not get integrated in the host chromosome upon the infection of mutant cells, as demonstrated by DNA-DNA hybridization experiments. In the case of prophage induction in mutant cells, as opposed to the wild type cells early mRNA synthesis is practically fully inhibited while the total RNA synthesis is three times reduced after 20 min of induction. The transcription of phage DNA associated with the changed superhelicity of DNA in the cell.
Mol Gen Mikrobiol Virusol 1985 Jun
PMID:[Development of bacteriophage Mu in E. coli gyrBts mutant strain]. 302 11

We have analyzed the structure of complexes between DNA gyrase and four defined DNA fragments by electric dichroism. Both the extrapolated dichroism and relaxation time of these complexes suggest that a single turn of DNA is wrapped around the enzyme with the entry and exit points located close together. The average angle between the DNA tails emerging from the particle is about 120 degrees. This structure is consistent with that seen by electron microscopy. Addition of ATP or the non-hydrolyzable ATP analog 5'-adenylyl-beta, gamma-imidodiphosphate results in a structural change of the complex, consistent with the DNA tails now being wrapped around the protein. The significance of these observations with respect to the mechanism of DNA supercoiling by DNA gyrase is discussed.
J Mol Biol 1987 Feb 05
PMID:Structure of the DNA gyrase-DNA complex as revealed by transient electric dichroism. 303 96

We used site-specific recombination catalyzed by the bacteriophage lambda Int system to probe DNA structure and metabolism in vivo. In vitro, the complexity of catenated products was linearly proportional to substrate supercoil density. A system was developed that gave efficient, controlled Int recombination in Escherichia coli cells. From a comparison of the data obtained in vitro and in vivo, we conclude that Int recombination does have the same mechanism in vivo as it has in vitro, but that only 40% of the plasmid DNA linking deficit in E. coli cells may be in the interwound supercoil form demonstrated in vitro. We suggest that this is the effective level of supercoiling in vivo, because the remaining DNA is constrained in alternative forms by protein binding. The study of Int recombination in vivo also provides an assay for enzymes that decatenate circular molecules, such as those formed during DNA replication. We find that DNA gyrase is the principal decatenase in E. coli and that it acts spontaneously and rapidly.
J Mol Biol 1987 Mar 20
PMID:Use of site-specific recombination as a probe of DNA structure and metabolism in vivo. 303 50

When the dnaB37 initiation mutant of Bacillus subtilis is returned to a permissive temperature following a period at 45 degrees C, a synchronous round of DNA replication immediately ensues. Using this system we have been able to analyse the first fragments to be replicated while avoiding the use of thymine starvation or inhibitors of DNA replication. Such treatments are necessary to achieve even modest synchrony in germinating spores. Our results showed that the first fragment to be replicated was a 4 kb BamHI-SalI restriction fragment, BS6. In contrast, when the analysis was performed out in the presence of novobiocin, an inhibitor of DNA gyrase, replication from BS6 was inhibited and the first fragment to be replicated was BS5, a 5.6 kb fragment located 1.7 kb to the right of BS6. Replication from both putative origins was suppressed by rifamycin and was dependent upon dnaB. The results are discussed in relation to previous attempts to identify the first replicating fragment in germinating spores. We also discuss the possibility that B. subtilis contains two origins and suggest that either can act as the primary origin under certain conditions, or alternatively that both origins may act in concert in normal bidirectional replication, each site being required for the leading strand in each direction.
Mol Gen Genet 1987 Jun
PMID:Chromosomal initiation in Bacillus subtilis may involve two closely linked origins. 303 10

The highly defective rho-15 mutant of Escherichia coli produces plasmid DNA that is 22% less negatively supercoiled than DNA from an isogenic wild-type strain (J. S. Fassler, G. F. Arnold, and I. Tessman, Mol. Gen. Genet. 204:424-429, 1986). We extended our measurements of plasmid superhelicity to additional rho mutants and to strains containing mutations that suppress rho transcription termination defects; the suppressor mutations were in the rpoB and the rho genes. The superhelicity of plasmid DNA was reduced by 11 and 10%, respectively, in the rho-702 and rho-201 mutants, both of which are less defective in Rho-mediated transcription termination than rho-15. Plasmid superhelicity was restored in all the suppressed rho mutants; in one rpoB mutant, plasmid DNA was even more negatively supercoiled than in rpoB+ cells, whether in a rho+ or rho mutant background. Suppression of rho mutants enabled them to maintain plasmids that could not be maintained in the mutants in the absence of the suppressor mutations. The results indicate that in addition to DNA gyrase, topoisomerase I, and Rho, RNA polymerase is also a determinant of DNA superhelicity, and its effect is modified by the Rho protein. We propose that Rho may increase the degree of DNA unwinding by the transcription complex, possibly at transcription termination sites.
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PMID:Regulation of DNA superhelicity by rpoB mutations that suppress defective Rho-mediated transcription termination in Escherichia coli. 304 90

Restriction fragments containing either leut (a rho-independent transcription termination site) and/or leut' (a rho-dependent transcription termination site) were cloned into plasmid pOL4. Treatment of plasmid-containing Escherichia coli strains with coumermycin resulted in loss of in vivo plasmid superhelicity 10 min after antibiotic addition. Galactokinase levels specified by these plasmid-containing strains were the same regardless of whether functional DNA gyrase was present. These results suggest that transcription termination is unaffected by the superhelical state of DNA.
Mol Gen Genet 1987 May
PMID:Effect of DNA superhelicity on transcription termination. 330

Induction of the SOS genes is required for efficient repair of damaged DNA in Escherichia coli. SOS induction by nalidixic acid or oxolinic acid, two inhibitors of DNA gyrase, requires the RecBC enzyme of E. coli. We report here that the nuclease activity of RecBC enzyme is not needed for SOS induction by these agents. We suggest that the unwinding activity of RecBC enzyme produces single-stranded DNA which activates the RecA protein to stimulate LexA repressor cleavage and SOS induction.
Mol Gen Genet 1985
PMID:Role of Escherichia coli RecBC enzyme in SOS induction. 391 Oct 29

A 140 base-pair DNA segment situated just upstream of the kanamycin resistance gene of transposon Tn2350, a transposon carried by the plasmid R1, was found to act as an origin of replication and allow autonomous replication of a plasmid composed only of the segment and of the tetracycline resistance gene of pBR322. This segment also promotes site-specific recombination: when cloned in pBR322 it promotes multimer formation in a recA- strain. If two copies are cloned on the same plasmid they promote either deletion or inversion of the intervening region, depending on their orientation relative to each other. DNA gyrase seems to be involved in this process since the inversion rate, in a plasmid carrying sequences in opposite orientations, varies in different nalidixic acid-resistant strains (gyr A mutants) independently isolated.
J Mol Biol 1984 Sep 05
PMID:A 140 base-pair DNA segment from the kanamycin resistance region of plasmid R1 acts as an origin of replication and promotes site-specific recombination. 609 Jun 78


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