Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.3 (topoisomerase)
 9,911 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aryl-fluoroquinolone derivatives A-56619 (difloxacin) and A-56620 were found to inhibit human peripheral blood mononuclear cell (MNC) proliferation (measured by [3H]thymidine uptake) that was induced by concanavalin A or monoclonal antibody OKT3. These antimicrobial agents exert their maximum suppressive effect when added within the first 24 h after the onset of culture with concanavalin A. No increase in the concentration of mitogen or the duration of incubation of MNC cultures reversed this inhibitory effect, but the removal of the drug from cultures reversed the suppression of DNA synthesis. A-56619 appeared not to interfere with the triggering of MNC activation by mitogen because it did not inhibit mitogen-induced increase in protein synthesis (measured by [3H]leucine incorporation), interleukin-2 receptor expression (measured by the binding of fluorescein-conjugated monoclonal antibody against interleukin-2 receptor), and cell volume. These findings are considered in terms of possible interference of aryl-fluoroquinolones with mammalian topoisomerase and DNA polymerases.
Antimicrob Agents Chemother 1986 Sep
PMID:Aryl-fluoroquinolone derivatives A-56619 (difloxacin) and A-56620 inhibit mitogen-induced human mononuclear cell proliferation. 309 95

B. subtilis mutants resistant to novobiocin that were selected after treatment of the strain SB25 by nitrosoguanidine acquired the slow growth, increased UV-sensitivity, the low frequency of homologous recombination in transduction and transformation. The mutant strains are characterized by the low activity of the double stranded DNA-dependent ATP-ase peculiar for cells with impaired B-subunit of DNA-gyrase.
Mol Gen Mikrobiol Virusol 1988 Sep
PMID:[Reduced frequency of homologous recombination in Bacillus subtilis mutants resistant to novobiocin]. 314 19

The frequency of sister-chromatid exchanges (SCE) was studied in peripheral blood lymphocytes from a xeroderma pigmentosum (form II, XPII) patient. The cells were irradiated with UV or X-rays. In some experiments novobiocin (NB), inhibitor of topoisomerase II, or caffeine (CA), inhibitor of DNA repair were added to the cultures. The level of spontaneous SCE in the patient's lymphocytes was found to be significantly increased in comparison to that in the cells from normal donors. The inhibitors and UV-light caused a rise in the frequency of SCE in the cells taken from normal donors and except for NB, in the lymphocytes from the patient XPII. X-Rays did not increase SCE frequency in normal lymphocytes and lowered it in the patient's cells. SCE frequency rose when inhibitors of DNA replication and repair were used in combination with mutagens.
Mutat Res 1987 Sep
PMID:Sister-chromatid exchanges in a special form of xeroderma pigmentosum (form II). 362 39

Changes in sensitivity of mouse BALB/c 3T3 cells in the plateau phase to digestion with micrococcal nuclease were examined following gamma-irradiation. Immediately after irradiation, cell nuclei were more sensitive to micrococcal nuclease compared to unirradiated nuclei. However, there were no detectable changes in length of basic repeating subunits of 182 base pairs of DNA, which include the nucleosome cores consisting of approximately 140 base pairs of DNA, which When the cells were incubated at 37 degrees following irradiation, the sensitivity of cell nuclei to the nuclease first increased then decreased, reaching a similar level to unirradiated nuclei 6 h after irradiation. Both the initial increase and the subsequent decrease in sensitivity of nuclei to micrococcal nuclease were prevented when 15 microM novobiocin was present during the post-irradiation incubation, suggesting a possible involvement of type II DNA topoisomerase in repair of DNA lesions induced by gamma-rays.
Int J Radiat Biol Relat Stud Phys Chem Med 1985 Sep
PMID:Changes in nuclease sensitivity of mammalian cells after irradiation with 60Co gamma-rays. 387 79

The concerted action of DNA gyrase and RecA protein of Escherichia coli on intact and gapped homologous or partially homologous plasmid DNA molecules leads to the formation of covalently closed DNA containing one strand of each parental molecule. Large regions of non-homology can be incorporated into the closed circular duplex. Both proteins are essential for the reaction to take place, and type I topoisomerase cannot substitute for DNA gyrase.
EMBO J 1984 Sep
PMID:Formation of covalently closed heteroduplex DNA by the combined action of gyrase and RecA protein. 609 61

Escherichia coli DNA gyrase contains a 1:1 ratio of protomers coded by the genes gyrA and gyrB. This along with previous results shows that the enzyme has two copies of each protomer and thus a molecular weight of 400,000. Abortion of the gyrase reaction results in double-strand breakage of the DNA and covalent attachment of both gyrA protomers to the 5'-cut ends. We conclude that the gyrA protomer contains a critical part of the active site for the concerted breakage and reunion reaction of gyrase, the topoisomerase activity of the enzyme.
Nucleic Acids Res 1980 Sep 11
PMID:DNA gyrase subunit stoichiometry and the covalent attachment of subunit A to DNA during DNA cleavage. 625 21

A purified preparation of the Escherichia coli integration host factor (IHF) displays two polypeptides of apparent molecular weight 11,000 and 9,500 when analyzed by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Under nondenaturing conditions, IHF appears to exist as a 1:1 complex of these two polypeptides. Integrative recombination takes place in vitro when purified IHF and purified Int, a product of a bacteriophage lambda gene, are the only proteins added to reaction mixtures. No recombination is detected in the absence of either protein. The characteristics of the recombination reaction carried out by these two purified proteins are described. Purified IHF binds to DNA; in the presence of Int, a ternary complex is formed at one of the specific recombination sites. IHF hs no detectable endonuclease or topoisomerase activity. Several possibilities for the role of IHF in recombination are considered.
J Biol Chem 1981 Sep 10
PMID:Purification and properties of the Escherichia coli protein factor required for lambda integrative recombination. 626 68

Using kinetoplast DNA networks as a substrate in a decatenation assay, we have purified to apparent homogeneity a type II DNA topoisomerase from HeLa cell nuclei. The most pure preparations contain a single polypeptide of 172,000 daltons as determined by sodium dodecyl sulfate-gel electrophoresis. The molecular weight of the native protein, based on sedimentation and gel filtration analyses, is estimated to be 309,000. These results suggest that the enzyme is a dimer of 172,0090-dalton subunits. The enzyme is a type II topoisomerase as demonstrated by its ability to change the linking number of DNA circles in steps of two and to decatenate or unknot covalently closed DNA circles. No gyrase activity is detectable. ATP is required for the relaxation, decatenation, and unknotting of DNA, and a DNA-dependent ATPase activity is present in the most pure fractions. ATP is hydrolyzed to ADP in this properties to T4 DNA topoisomerase (Liu, L. F., Liu, C. C., and Alberts, B. M. (1979) Nature 281, 456-461).
J Biol Chem 1981 Sep 10
PMID:A homogeneous type II DNA topoisomerase from HeLa cell nuclei. 626 71

Type I DNA topoisomerases from mouse ascites cell nuclei and from rat liver cell nuclei act on denatured viral closed circular PM2 DNA to produce molecules with a highly contracted structure as well as fully duplex non-supercoiled covalently closed circular molecules. Highly contracted DNA molecules contain a novel type of topological linkage in which a strand in one region of the double-stranded molecule passes between the strands in another region of the circular molecule one or more times. Since it is also found that the action of the topoisomerase promotes renaturation of complementary strands in denatured closed circular DNA, it is suggested that formation of contracted DNA structures proceeds through renatured, duplex intermediates with highly negative superhelix densities that contain small single-stranded regions.
Biochim Biophys Acta 1981 Sep 28
PMID:Type I DNA topoisomerases from mammalian cell nuclei interlock strains and promote renaturation of denatured closed circular PM2 DNA. 626 25

When SV40-infected cells are placed into hypertonic medium, newly synthesized DNA accumulates as form C catenated dimers. These molecules consist of two supercoiled monomer circles of SV40 DNA interlocked by one or more topological inter-twinings and are seen as transiently labeled inter-mediates during normal replication. Form C catenated dimers represent pure segregation intermediates, replicative DNA structures in which DNA synthesis is complete but which still require topological separation of the two daughter circles. Hypertonic shock seems to block selectively a type II topoisomerase activity involved in disentangling the two circles. This is reflected in the fact that form C catenated dimers that accumulate during the block are highly intertwined with catenation linkage numbers up to C(L) = 20. While initiation of replication is also inhibited by hypertonic treatment, ongoing SV40 DNA synthesis is not affected, and replication is free to proceed from the earliest cairns structure through to form C catenated dimers. The block to segregation is rapidly and completely released by shifting the cells back to normal medium. A much slower recovery of DNA segregation takes place on prolonged incubation in hypertonic medium, perhaps because of some cellular homeostatic mechanism. The results of this work lead to a detailed view of the final stages of SV40 DNA replication.
Cell 1981 Sep
PMID:Arrest of segregation leads to accumulation of highly intertwined catenated dimers: dissection of the final stages of SV40 DNA replication. 626 52


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