Patrick O. Brown, Craig L. Peebles, Nicholas R. Cozzarelli,
We have identified a topoisomerase activity from Escherichia coli related to DNA gyrase (topoisomerase II): we designate it topoisomerase II'. It was constructed of two subunits, which ... peptide maps of the two subunits are similar. Topoisomerase II' relaxes negatively supercoiled DNA and, uniquely among E. coli topoisomerases, relaxes positive supercoils efficiently. It is the only topoisomerase that can introduce positive supercoils; these are stoichiometric with enzyme molecules. Topoisomerase II' resembles gyrase in its sensitivity to oxolinic ...
Tópico(s): Bioactive Compounds and Antitumor Agents
1979 - National Academy of Sciences | Proceedings of the National Academy of Sciences
C. C. Cheng, Robert K. Y. Zee-Cheng, V. L. Narayanan, Robert B. Ing, K. Pauli,
... antimicrobial agents. Despite their promising target characteristics, only topoisomerase II inhibitors targeting DNA gyrase and/or topoisomerase IV have reached clinical use. Topoisomerases are the enzymes that are essential for cellular ... and synthetic compounds have been identified as potential topoisomerase inhibitors but the resistance is most commonly found ... increased the need for the development of novel topoisomerase inhibitors with efficacy and high potency against FQ- ... modifications of existing FQ scaffolds, novel non-quinolone topoisomerase II inhibitors, known as novel bacterial topoisomerase inhibitors, ...
Tópico(s): Microwave-Assisted Synthesis and Applications
1981 - Elsevier BV | Trends in Pharmacological Sciences
DNA topoisomerases are enzymes that catalyze changes in the topological structure of DNA molecules. The basic chemical reaction carried out by topoisomerases is a cycle of breakage and rejoining of ... enzyme–DNA intermediate. There are two classes of topoisomerases—namely, (1) DNA topoisomerase I or ω protein and (2) type II topoisomerases. This chapter focuses on type II topoisomerases. Their basic mode of operation involves the generation ... the expense of ATP hydrolysis. Other type II topoisomerases stimulate the reverse reaction, converting supercoiled DNA to ...
Tópico(s): Gyrotron and Vacuum Electronics Research
1981 - Elsevier BV | The Enzymes
Leroy F. Liu, Kathryn G. Miller,
Two type I DNA topoisomerases have been purified to homogeneity from the nuclei of HeLa cells. One topoisomerase has a peptide molecular weight of 100,000 ... Several lines of evidence indicate that these two topoisomerases are closely related, (a) Both exhibit similar enzymatic ... DNA. (b) The chromatographic properties of the two topoisomerases during purification are similar. (c) Mild proteolysis of the purified molecular weight 100,000 topoisomerase in vitro generates a group of protein bands ... weight approximately 67,000, and these bands retain topoisomerase activity. (d) The peptides formed by partial proteolysis ...
Tópico(s): Synthesis and bioactivity of alkaloids
1981 - National Academy of Sciences | Proceedings of the National Academy of Sciences
... mixture of circular DNA and type I1 DNA topoisomerase purified from the embryos of Drosophila melanogaster.Similar ... the DNA knotting reaction by bacteriophage T4-induced topoisomerase (Liu, L. F., Liu, C. C., and Alberts, ... 697-707), the knotting reaction by the Drosophila topoisomerase 11 requires a high ratio of en- zyme/ ... knotted.The knotted DNA generated by the Drosophila topoisomerase I1 can be efficiently unknotted by a catalytic amount of Drosophila topoisomerase 11, but not by topoisomerase I.The ionic ...
Tópico(s): DNA Repair Mechanisms
1983 - Elsevier BV | Journal of Biological Chemistry
... demonstrate that the activity of the major DNA topoisomerase I from calf thymus is severely inhibited after ... poly(ADP-ribose) are covalently attached to DNA topoisomerase I. These observations with highly purified enzymes suggest ... may be a cellular mechanism for modulating DNA topoisomerase I activity in response to the state of ... ADP-ribosylation) of the Mr = 100,000 DNA topoisomerase I from calf thymus resulted in greater than ... poly(ADP-ribose) does not, by itself, inhibit topoisomerase activity. After modification, the apparent molecular weight of ...
Tópico(s): Synthesis and Biological Evaluation
1984 - Elsevier BV | Journal of Biological Chemistry
Kuan‐Chih Chow, George D. Pearson,
... developed a specific, sensitive, and quantitative assay for topoisomerase I, which is based on the formation of ... of 32P radioactivity from 32P-labeled DNA to topoisomerase I. Since 32P-labeled topoisomerase molecules are resolved by NaDodSO4/PAGE, HeLa topoisomerase I (100 kDa) and calf thymus topoisomerase I (82 kDa) can be quantitatively assayed in ... at least 0.3 ng (3 fmol) of topoisomerase I. We have used our assay to measure the levels of topoisomerase I activity in crude extracts of nuclei prepared ...
Tópico(s): Viral gastroenteritis research and epidemiology
1985 - National Academy of Sciences | Proceedings of the National Academy of Sciences
Joseph A. Holden, Robert L. Low,
... used to quantitate activity. In this reaction, DNA topoisomerase I relaxes the input supercoiled DNA to provide DNA topoisomerase II, a strongly favored template for catenation. DNA topoisomerase II preferentially catenates relaxed DNA over supercoiled DNA ... a factor of 100. One molecule of DNA topoisomerase II is able to catenate about 20 circles ... min at 30 degrees C. The purified HeLa topoisomerase I can also catenate DNA under these assay ... independent fashion. It is much less efficient than topoisomerase II; one molecule of topoisomerase I catenates only ...
Tópico(s): DNA Repair Mechanisms
1985 - Elsevier BV | Journal of Biological Chemistry
... antitumor and antibacterial agents inhibit type II DNA topoisomerases, yielding, in each case, a complex of enzyme ... inhibitor action by using the type II DNA topoisomerase of bacteriophage T4 as a model. The T4 topoisomerase is the target of antitumor agent 4'-(9- ... previously isolated, one with a point mutation in topoisomerase subunit gene 39 and the other with a point mutation in topoisomerase subunit gene 52. We report here that the wild-type T4 topoisomerase is inhibited by six additional antitumor agents that ...
Tópico(s): Neutropenia and Cancer Infections
1990 - Elsevier BV | Journal of Biological Chemistry
Karsten Wassermann, Judit Markovits, Christine Jaxel, Giovanni Capranico, Kurt W. Kohn, Yves Pommier,
... were studied on purified mouse leukemia (L1210) DNA topoisomerases I and II. DNA unwinding and cross-linking ... and Actinomycin D (but not doxorubicin) stimulated DNA topoisomerase I-induced cleavage at specific DNA sites; 2) ... and Actinomycin D stimulated DNA cleavage by DNA topoisomerase II; 3) at higher drug concentrations, DNA intercalators suppressed enzyme-mediated DNA cleavage induced by DNA topoisomerase I, as well as topoisomerase II; 4) only cyanomorpholinyldoxorubicin produced DNA-DNA cross- ...
Tópico(s): Bioactive Compounds and Antitumor Agents
1990 - American Society for Pharmacology and Experimental Therapeutics | Molecular Pharmacology
Jerome Schaak, Paul Schedl, Thomas Shenk,
The requirements for topoisomerases in transcription of adenovirus and HeLa cell genes were analyzed using drugs that specifically inhibit either topoisomerases I or II. Cleavage of viral DNA by topoisomerases in the presence of either camptothecin or VM26 ... ligation in the cleavage and ligation step of topoisomerase I or II respectively. Inhibition of topoisomerase II with VM26 did not cause a direct ... RNAs. Treatment of cells with camptothecin to inhibit topoisomerase I reduced but did not abolish transcription of ...
Tópico(s): Polyomavirus and related diseases
1990 - Oxford University Press | Nucleic Acids Research
Robert Hertzberg, Robert Busby, Mary Jo Caranfa, Kenneth G. Holden, Randall K. Johnson, Sidney M. Hecht, William D. Kingsbury,
... stabilizes, the cleavable complex formed between DNA and topoisomerase I. The nature of the interaction of CPT with the DNA-topoisomerase I binary complex was studied by the use ... compounds have been shown to trap the DNA-topoisomerase I complex irreversibly. Although cleavage of DNA plasmid mediated by topoisomerase I and camptothecin was reduced significantly by treatment ... h after similar treatment. The production of irreversible topoisomerase I-DNA cleavage was time-dependent, suggesting that ... employed [3H]BrCPT, which was shown to label topoisomerase I within the enzyme-DNA complex. [3H]BrCPT ...
Tópico(s): Synthesis and bioactivity of alkaloids
1990 - Elsevier BV | Journal of Biological Chemistry
Wai-Kwong Eng, F L McCabe, K. B. Tan, Michael R. Mattern, G A Hofmann, Richard Woessner, Robert Hertzberg, Richard K. Johnson,
... not cross-resistant to other antineoplastic agents, including topoisomerase II inhibitors. The type I topoisomerases purified from P388/CPT and P388/S cells ... cells than in the wild-type P388 cells. Topoisomerase I mRNA, immunoreactivity, and extractable enzymatic activity were ... P388/S cells. As resistance to camptothecin developed, topoisomerase I extractable activity decreased, concomitant with an increase in topoisomerase II extractable activity. Furthermore, the appearance of camptothecin resistance was associated with specific rearrangements of the topoisomerase I gene. These results suggest that development of ...
Tópico(s): DNA and Nucleic Acid Chemistry
1990 - American Society for Pharmacology and Experimental Therapeutics | Molecular Pharmacology
Douglas R. Boreham, A. Trivedi, Paul Weinberger, R. E. J. Mitchel,
... radiation resistance in yeast. Yeast mutants, deficient in topoisomerase I, in topoisomerase II, or in DNA polymerase I, were used ... inducible resistances. The absence of either or both topoisomerase activities did not prevent induction of either heat or radiation resistance. However, if both topoisomerase I and II activities were absent, the sensitivity ... stress) was markedly increased. The absence of only topoisomerase I activity (top1) resulted in the constitutive expression ... heat shock in wild-type cells, and the topoisomerase I-deficient cells were not further inducible by ...
Tópico(s): Genomics, phytochemicals, and oxidative stress
1990 - Radiation Research Society | Radiation Research
Jerome Schaack, Paul Schedl, Thomas Shenk,
Sites of topoisomerase I and II cleavage across large portions of the adenovirus type 5 genome were mapped by using the ... to DNA strand scission at the site of topoisomerase cleavage. Strong topoisomerase II cleavage sites occurred in clusters throughout the ... regions and transcriptional control regions. The efficiency of topoisomerase II cleavage increased as the rate of adenovirus ... transcription of the early viral genes. Positions of topoisomerase II cleavage sites did not vary during the infection. Topoisomerase I cleavage sites were also found throughout the ...
Tópico(s): Polyomavirus and related diseases
1990 - American Society for Microbiology | Journal of Virology
Steven N. Ebert, Svetlana Shtrom, Mark T. Muller,
... of recognition sites for eucaryotic DNA type II topoisomerase. Topoisomerase II sites were identified by means of the ... confirmed by sequencing DNA cleavages introduced by purified topoisomerase II. In vivo, host topoisomerase II also introduced double-stranded DNA breaks in ... at sites predicted by the consensus sequence. Host topoisomerase II acted on all immediate-early genes as ... and were most intense at 10 h postinfection. Topoisomerase II cleavages were not detected when viral DNA ... progeny viral genomes are acted upon by host topoisomerase II, this enzyme either does not act on ...
Tópico(s): Cytomegalovirus and herpesvirus research
1990 - American Society for Microbiology | Journal of Virology
Hong JH, Kosuke Okada, Toshihisa Kusano, Y Komazawa, M Kobayashi, Akiko Mizutani, N Kamada, Atsushi Kuramoto,
... restriction fragments showed that VP-16 stimulated DNA-topoisomerase II cleavable complex forming activity in crude nuclear ... two cell lines showed that mRNA levels of topoisomerase II in 50B-3 cells drastically decreased and ... m-AMSA, adriamycin. Thes findings suggest that reduced topoisomerase II activity (cellular levels) and cleavable complex forming ... significant factors in the marked drug resistance. DNA topoisomerase II / VP-16 / drag resistance. Réduction de topoisomérase II-ADN dans une lignée cellulaire de cancer ...
Tópico(s): Neutropenia and Cancer Infections
1990 - Elsevier BV | Biomedicine & Pharmacotherapy
Paul J. Smith, Sandra Bell, Alan Dee, Hazel Sykes,
... a pathway which can be blocked by DNA topoisomerase poisons. We have studied the relationship between ligand resistance and DNA topoisomerase II activity. The cross-sensitivity patterns of the ... m-anisidide (mAMSA)] and non-intercalating (VP16-213) topoisomerase II poisons. The mutant was cross-resistant to ... in: (i) the in vitro decatenation activity of topoisomerase II, (ii) VP16-213 or mAMSA induced protein— ... DNA strand scisson) in intact cells exposed to topoisomerase poisons. Ho33342 and the topoisomerase II inhibitor novobiocin ...
Tópico(s): Synthesis and Biological Evaluation
1990 - Oxford University Press | Carcinogenesis
The role of topoisomerases in the replication of human adenovirus type 5 was investigated with topoisomerase inhibitors. Both topoisomerase I and topoisomerase II inhibitors blocked adenovirus replication when added at ... infection. At late times after infection, camptothecin, a topoisomerase I inhibitor, inhibited adenovirus DNA replication and induced ... at defined regions of the viral genome. The topoisomerase II inhibitors, VP-16 (etoposide) and ellipticine, did ... 17:3535-3550, 1989), was inhibited by the topoisomerase II inhibitors. Transcription of adenovirus major late genes ...
Tópico(s): Bacteriophages and microbial interactions
1990 - American Society for Microbiology | Journal of Virology
Kuan‐Chih Chow, Warren E. Ross,
The nuclear enzyme DNA topoisomerase II catalyzes the breakage and resealing of duplex DNA and plays an important role in several genetic processes. It also ... as etoposide. We have examined the activity of topoisomerase II during the first cell cycle of quiescent ... in vivo was used as a parameter of topoisomerase II activity, and enzyme content was assayed by ... sensitivity was associated with an increase in intracellular topoisomerase II content as determined by immunoblotting. The induction of topoisomerase II-mediated drug sensitivity was aborted within 1 ...
Tópico(s): DNA Repair Mechanisms
1987 - Taylor & Francis | Molecular and Cellular Biology
Yang Liu, Marc S. Wold, J J Li, Thomas J. Kelly, Leroy F. Liu,
We examined the roles of DNA topoisomerases in the replication of simian virus 40 (SV40) DNA in a cell-free system composed of an extract from HeLa cells supplemented ... SV40 tumor antigen. When the activities of both topoisomerase I (EC 5.99.1.2) and topoisomerase II (EC 5.99.1.3) in the ... of 15-20. Addition of purified HeLa DNA topoisomerase II to extracts immunologically depleted of both topoisomerases completely restored replication, and the replication products consisted ... monomeric daughter molecules. Addition of purified HeLa DNA topoisomerase I to depleted extracts restored DNA synthesis, but ...
Tópico(s): Bacteriophages and microbial interactions
1987 - National Academy of Sciences | Proceedings of the National Academy of Sciences
Jeffrey M. Besterman, Lynn P. Elwell, Steven G. Blanchard, Michael Cory,
... culture. Recent evidence indicates that the enzyme, DNA topoisomerase II, is probably required for DNA synthesis to ... inhibited both the catalytic activity of purified DNA topoisomerase II in vitro and DNA topoisomerase II-dependent cell functions in vivo. Many compounds capable of inhibiting DNA topoisomerase II are DNA intercalators. Thus, we performed studies ... cleavage of DNA in the presence of DNA topoisomerase II, indicating that the mechanism by which amiloride inhibited DNA topoisomerase II was not through the stabilization of a ...
Tópico(s): DNA and Nucleic Acid Chemistry
1987 - Elsevier BV | Journal of Biological Chemistry
Kuan‐Chih Chow, Warren E. Ross,
The nuclear enzyme DNA topoisomerase II catalyzes the breakage and resealing of duplex DNA and plays an important role in several genetic processes. It also ... as etoposide. We have examined the activity of topoisomerase II during the first cell cycle of quiescent ... in vivo was used as a parameter of topoisomerase II activity, and enzyme content was assayed by ... sensitivity was associated with an increase in intracellular topoisomerase II content as determined by immunoblotting. The induction of topoisomerase II-mediated drug sensitivity was aborted within 1 ...
Tópico(s): Polyomavirus and related diseases
1987 - Taylor & Francis | Molecular and Cellular Biology
David S. Gilmour, Gert O. Pflugfelder, James C. Wang, John T. Lis,
The in vivo distribution of topoisomerase I on specific DNA sequences is determined at high resolution in Drosophila cells using a photo-crosslinking method. Topoisomerase I-DNA adducts are generated by irradiation of ... and then purified by immunoprecipitation with antibody to topoisomerase I. Analyses of the DNA sequences crosslinked to topoisomerase I by blot-hybridization with appropriate DNA probes indicate that topoisomerase I is concentrated on transcribed regions and not on nontranscribed flanking sequences. Like RNA polymerase II, topoisomerase I is recruited to heat-shock genes during ...
Tópico(s): DNA Repair Mechanisms
1986 - Cell Press | Cell
... affect the breakage-rejoining reaction of mammalian DNA topoisomerase II by trapping a covalent enzyme-DNA cleavable ... mechanism of cell killing by anticancer drugs. DNA topoisomerase may be a key component in the regulation of chromatin conformation and cell proliferation. DNA topoisomerases are enzymes that control the topology of DNA. ... recombination. Based on their mechanism of action, DNA topoisomerases have been categorized into two types. Type I and type II DNA topoisomerases catalyze the topological changes in DNA by transiently ...
Tópico(s): Synthesis and bioactivity of alkaloids
1986 - Elsevier BV | Annual reports in medicinal chemistry
Renu A. Heller, Earl R. Shelton, V. Dietrich, Sarah C. R. Elgin, Douglas L. Brutlag,
Purified type I1 topoisomerase from Drosophila meyotic type I1 topoisomerase, DNA gyrase, is to induce negative lanogaster embryos was reported earlier to contain ... Osheroff, N. and D* L. karyotic type I1 topoisomerases is their subunit structure.(1983) J-B i ... a tetramer 'containing two A subunits of fied topoisomerase I1 we have raised antibodies against 105,000 ... imme-each mediates a different part of the topoisomerase reaction.diately upon lysis.Using antigen-dfinity purified ... is inhibited tibody from the cluster of purified topoisomerase 11 by the antibiotic nalidixic acid.The B ...
Tópico(s): Protist diversity and phylogeny
1986 - Elsevier BV | Journal of Biological Chemistry
The role of DNA topoisomerases in eucaryotic class III gene transcription in vitro has been studied through the use of inhibitory drugs and antisera to DNA topoisomerases I and II. The DNA topoisomerase II inhibitors, novobiocin and coumermycin AI, were found ... this step reflects the enzymatic action of DNA topoisomerase II since a specific inhibitor of this enzyme (VM-26) and anti-DNA topoisomerase II antibodies fail to inhibit transcription under conditions where topoisomerase II enzymatic activity is inhibited. Similarly, a specific ...
Tópico(s): DNA Repair Mechanisms
1986 - Oxford University Press | Nucleic Acids Research
Wai-Kwong Eng, Subrata Pandit, Rolf Sternglanz,
DNA topoisomerase I from the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe was overproduced using the cloned genes. Extracts from cells overproducing DNA topoisomerase I were prepared and incubated with 32P-labeled DNA. Alkali was used to trap the topoisomerase I-DNA covalent intermediate. Most of the DNA ... digested with nuclease, and the resultant 32P-labeled topoisomerase I was subjected to cleavage with cyanogen bromide ... that the active site tyrosine of eukaryotic DNA topoisomerase I is very near the carboxyl terminus, at ...
Tópico(s): DNA Repair Mechanisms
1989 - Elsevier BV | Journal of Biological Chemistry
L D Gorsky, Simone Cross, M. Morin,
... to suggest that protein kinase C and DNA topoisomerases are functionally linked in signal transduction pathways. Much ... is based on the observation that phosphorylation of topoisomerase II by protein kinase C may lead to its activation in vitro and that inhibitors of topoisomerase II block phorbol diester-induced differentiation in HL- ... the present study, the activities of the DNA topoisomerases I and II have been quantitated to examine ... HL-60 cells undergoing differentiation. The activity of topoisomerase I increased rapidly after treatment with phorbol myristate ...
Tópico(s): Acute Lymphoblastic Leukemia research
1989 - Pergamon Press | Cancer Communications