Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:5.99.1.2 (topoisomerase)
9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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).
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PMID:A homogeneous type II DNA topoisomerase from HeLa cell nuclei. 626 71

In cells of Fanconi's anemia (FA) spontaneous breakage of chromosomes was first recognized by Schroeder et al. (1964). Sensitivity to bivalent alkylants has been found to be a constant feature, whereas low levels of several repair-related enzymes have been described in different FA cell lines. In a family with known FA, during a further pregnancy the prenatal diagnosis of the disease was made by cytogenetic analysis of amniotic cells. After birth the fresh placenta was extracted for further enzymologic analysis. An unusual distribution of DNA topoisomerase activity was noted: high in the cytoplasm and only a little activity in the nuclear sap. This contrasts with findings in normal placentae. Since amniotic cells, lymphocytes, and fibroblasts of this child exhibited both high spontaneous breakage of chromosomes and sensitivity to the bivalent alkylant, diepoxybutane, a correlation between the findings on cytogenetic and enzymologic levels is assumed. Whereas in other published cases, a true reduction of activities of enzymes involved in DNA replication and repair has been found, the present results suggest the interpretation that in our patient the genetic anomaly does not affect the level of synthesis of the enzyme itself, but the passage of the enzyme from the place of synthesis (the cytoplasm) to the substrate (inside the nucleus). A genetic anomaly of the nuclear membrane might be a possible explanation, or alternatively, a structural mutation of the enzyme at a site not affecting the catalytic activity, but affecting the membrane passage or intranuclear accumulation. Meanwhile, placentae of two other cases gave similar results, thus supporting our findings.
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PMID:Fanconi's anemia: anomaly of enzyme passage through the nuclear membrane? Anomalous intracellular distribution of topoisomerase activity in placental extracts in a case of Fanconi's anemia. 626 89

Bacteriophage T4 DNA topoisomerase has been isolated and shown to contain the proteins coded by the DNA-delay genes 39 and 52 (Liu, L. F., Liu, C.-C., and Alberts, B. M. (1979) Nature (Lond.) 281, 456-461 and Stetler, G. L., King, G. J., and Huang, W. M. (1979) Proc. Natl. Acad. Sci. U. S. A. 76, 3737-3741). From complementation measurements in vitro and from earlier genetic evidence, these workers suggested that the product of gene 60 (p60) was also a component of the DNA topoisomerase complex. This paper now establishes the identity of p60 and unequivocally shows that this protein is a component of the enzyme complex. T4 DNA topoisomerase was purified by a simplified two-column procedure and found to be a stable complex of p39, p52, and a protein with a relative molecular weight of 18,000. The 18,000-dalton chain has been unambiguously shown to be the product of gene 60 through the use of an amber mutant of gene 60 with Sup+ and Sup- hosts and analyses by two-dimensional gel electrophoresis. While p39 and p52 were tightly associated in the wild type enzyme complex, they were readily separated on a hydroxylapatite column from extracts of cells infected by an amber mutant of gene 60. These findings suggest that p60 plays a structural/functional role in the enzyme complex by holding the larger p39 and p52 in juxtaposition.
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PMID:Identification of bacteriophage T4 gene 60 product and a role for this protein in DNA topoisomerase. 629 73

A DNA topoisomerase activity is found to be associated with the nucleosomes released by the Staphylococcal nuclease digestion of HeLa nuclei. Such an association is found to be salt dependent. A number of criteria have established that this DNA topoisomerase activity is due to HeLa topo I (Liu, L. F. and Miller, K. G. (1980) Proc. Natl. Acad. Sci. USA 78, 3489-3491). A similar association has been demonstrated from the in vitro studies using purified mononucleosomes and eukaryotic DNA topoisomerase I. Nonhistone HMG proteins and histone H1 are found to stimulate topoisomerase activity in vitro and form tight complexes with eukaryotic DNA topoisomerase I. The intimate interactions of topoisomerase I with chromosomal proteins and nucleosomes may be an essential feature of the topoisomerase function in vivo.
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PMID:Association of eukaryotic DNA topoisomerase I with nucleosomes and chromosomal proteins. 629 26

Besides the nicking-closing (topoisomerase I) activity, an ATP-dependent DNA topoisomerase is present in rat liver nuclei. The enzyme, partially purified, is able to catenate in vitro closed DNA circles in a magnesium-dependent, ATP-dependent, histone H1-dependent reaction, and to decatenate in vitro kinetoplast DNA networks to yield free minicircles in a magnesium-dependent and ATP-dependent reaction. It is largely similar to other eukaryotic type II topoisomerases in its requirements, and presumably belongs to this class of enzymes. Type I and type II activities were measured in rat liver nuclei as a function of regenerating time after partial hepatectomy: type I activity was not significantly changed during this process. In contrast, type II activity was considerably increased, suggesting a possible involvement of the enzyme in DNA replication.
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PMID:DNA topoisomerases from rat liver: physiological variations. 629 30

A DNA topoisomerase activity, copurifying with poly(ADP-ribose) synthetase from calf thymus, is greater than 95% inhibited if extensive poly(ADP-ribosylation) is allowed to occur. The inhibited DNA topoisomerase, which has drastically different elution properties on hydroxylapatite, can be reactivated by mild alkaline treatment. These results are consistent with a poly(ADP-ribosylation) of the DNA topoisomerase and covalent attachment of the poly(ADP-ribose) moieties to the topoisomerase by alkali-labile bonds.
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PMID:Poly(ADP-ribosylation) of a DNA topoisomerase. 630 23

DNA topoisomerase activity detected in cell extracts of the trypanosomatid Crithidia fasciculata interlocks kinetoplast DNA duplex minicircles into huge catenane forms resembling the natural kinetoplast DNA networks found in trypanosomes. Catenation of duplex DNA circles is reversible and equilibrium is affected by ionic strength, and by spermidine. The reaction requires magnesium, is ATP dependent and is inhibited by high concentrations of novobiocin. Extensive homology between duplex DNA rings was not required for catenane formation since DNA circles with unrelated sequences could be interlocked into mixed network forms. Covalently sealed catenaned DNA circles are specifically used as substrates for decatenation. No such preference for covalently sealed duplex DNA rings was observed for catenate formation. Its catalytic properties and DNA substrate preference, suggest a potential role for this eukaryotic topoisomerase activity in the replication of kinetoplast DNA.
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PMID:Reversible decatenation of kinetoplast DNA by a DNA topoisomerase from trypanosomatids. 630 72

A protein required for the elongation of replicating intermediates of adenovirus (Ad) DNA to full length has been isolated and characterized. This factor, isolated from nuclear extracts of uninfected HeLa cells, has been designated nuclear factor II. In the presence of Ad DNA with proteins at each 5' end (Ad DNA-protein) and three proteins coded for by the Ad genome [the preterminal protein (pTP), the DNA polymerase (Ad Pol), and the DNA binding protein (Ad DBP)], nuclear factor II complementing activity is detected only in the presence of host nuclear factor I. Highly purified preparations of nuclear factor II that are free of detectable DNA polymerase alpha, beta, and gamma activities contain a DNA topoisomerase activity. Furthermore, type I DNA topoisomerases purified from HeLa cells and calf thymus substitute for nuclear factor II complementing activity in the in vitro Ad DNA replication system. These results indicate that a protein that is involved in higher order DNA structure is required for Ad replication. This protein plus the purified proteins described above carry out the initiation and synthesis of full-length 36,000-base-pair Ad DNA.
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PMID:Adenovirus DNA replication in vitro: synthesis of full-length DNA with purified proteins. 630 11

Nuclear novobiocin binding proteins (NBPs) from a set of mouse L cells have been extensively purified by affinity chromatography on novobiocin-Sepharose columns. The NBPs, specifically eluted with 100 micrograms of novobiocin per ml, exhibited equivalent DNA topoisomerase activities (measured as ATP-dependent relaxation or catenation of phi X174 replicative-form I DNA substrate) when extracted from equal numbers of wild-type (WT-4) mouse L cells growing logarithmically at 34 degrees C or at 38.5 degrees C, from ts A1S9 cells similarly cultivated at the low, permissive temperature or from revertant ts+ AR cells in exponential growth at either temperature. The NBPs isolated from similar numbers of ts A1S9 cells grown to midlogarithmic phase and then incubated for 24 hr at 38.5 degrees C (the nonpermissive temperature) showed no topoisomerase II activity. Preliminary NaDodSO4/polyacrylamide gel electrophoretic analysis of enzymatically active material revealed that the NBPs of WT-4 and ts+ AR cells grown at 34 degrees C comprised three major polypeptides of 76,000, 74,000, and 30,000 daltons and a number of larger molecular mass components present in trace amounts. The NBP of ts A1S9 cells grown at the permissive temperature was similar, except that the 30,000-kilodalton polypeptide was not detected. Such enzymatically active NBPs from WT-4 and ts+ AR cells were unaffected by 100 micrograms of novobiocin per ml, whereas the analogous preparation from ts A1S9 cells was totally inhibited. On the basis of these and other considerations, it is postulated that the ts A1S9 locus of mouse L cells encodes a temperature-sensitive polypeptide that is required for normal DNA topoisomerase II activity.
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PMID:ts A1S9 locus in mouse L cells may encode a novobiocin binding protein that is required for DNA topoisomerase II activity. 630 35

Inhibitors of bacterial DNA gyrase and eukaryotic DNA topoisomerase (novobiocin and nalidixic acid) were investigated with respect to their effect on the activity of RNA-dependent DNA polymerases from murine and avian retroviruses. Purified RNA-dependent DNA polymerase from AKR virus was inhibited more than 90% by 0.3 mg/ml and almost completely by 1 mg/ml of the drugs when poly(A) X oligo(dT)12-18 was used as a template-primer. In contrast to the enzyme from AKR virus, purified enzyme from avian myeloblastosis virus was less sensitive, i.e. nearly 50% activity remained even in the presence of 1 mg/ml of the drugs with the same template-primer. RNA-dependent DNA polymerase activity in AKR virus particles was inhibited, but was resistant to low concentrations of the drugs. The inhibition was not due to specific interaction between drugs and the template-primer or labelled precursor, since RNA-dependent DNA polymerase was inhibited by the drugs with activated calf thymus DNA or poly(C) X oligo(dG)12-18 as the template. Endogenous DNA synthesis by AKR virus particles was inhibited by novobiocin to the same extent.
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PMID:Inhibition of retrovirus RNA-dependent DNA polymerase by novobiocin and nalidixic acid. 631 59


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