Antigen Background Topoisomerase II alpha is an essential nuclear enzyme involved in DNA replication and is a target for many anti-cancer drugs used for cancer therapy. Decreased expression of topoisomerase II alpha is the predominant mechanism of resistance to several chemotherapeutic agents. A significant variation in the range of expression of this protein has been reported in many different tumors. Reports of the analysis of primary breast tumors have indicated that topoisomerase II beta is more widely expressed than topoisomerase II alpha. Topoisomerase II alpha expression and activity is linked to the cell cycle and is associated with the proliferation status of cells.. ...
Human Topoisomerase II Assay Kit available from TopoGEN - measure topo II activity in a crude extract. Highly specific and quantifiable.
Human Topoisomerase II Assay Kit available from TopoGEN - measure topo II activity in a crude extract. Highly specific and quantifiable.
TY - JOUR. T1 - Eukaryotic topoisomerase II preferentially cleaves alternating purine-pyrimidine repeats. AU - Spitzner, J. R.. AU - Chung, In Kwon. AU - Muller, M. T.. PY - 1990/1/11. Y1 - 1990/1/11. N2 - Alternating purine-pyrimidine sequences (RY repeats) demonstrate considerable homology to the consensus sequence for vertebrate topoisomerase II (Spitzner and Muller (1988) Nucleic Acids Res. 16: 1533-1556). This is shown below and positions that can match are underscored. (R is purine, Y is pyrimidine, K is G or T.) Topoisomerase II cleavage reactions were performed (in the absence of inhibitors) on a plasmid containing a 54 base RY repeat and the single strong cleavage site mapped to the RY repeat. Analysis of this DNA on sequencing gels showed that the enzyme cleaved a number of sites, all within the 54 base pair RY repeat. Topoisomerase II also made clustered cleavages within other RY repeats that were examined. Quantitative analysis of homology to the consensus sequence, as measured by ...
In yeast, a single copy of topo II is essential for chromosome segregation (Uemura et al., 1987). In the biochemical and immunological depletion study of Xenopus egg extracts, topo IIα was shown to be required for chromosome condensation, whereas the function of topo IIβ remained obscure because its localization and relative amount to topo IIα in the egg extracts were unknown (Hirano and Mitchison, 1993). In mammals, the role of topo IIα and topo IIβ, and their cellular localization, were extensively studied using specific mAbs against each isoform (Cobb et al., 1999; Tsutsui et al., 2001; Turley et al., 1997; Yabuki et al., 1996). This idea was challenged by the recent observation that there might exist residual but sizable amounts of heterodimers of topo IIα/topo IIβ in the cultured cell extract (Christensen et al., 2002).. The knocking-out of topo IIβ does not affect embryonic development because topo IIα can substitute for it until the birth of the fetus (Yang et al., 2000), ...
Head and neck cancer including oral cancer is considered to develop by accumulated genetic alterations and the major pathway is cancerization from lesions such as intraepithelial dysplasia in oral leukoplakia and erythroplakia. The relationship of proliferation markers with the grading of dysplasia is uncertain. The involvement of EBV in oral carcinogenesis is not fully understood. The present study was designed to investigate the role of EBV and DNA Topoisomerase II∝ (DNA-Topo II∝) during oral carcinogenesis and to examine the prognostic significance of these protein expressions in OSCCs. Using specific antibodies for EBV and DNA-Topo II∝, we examined protein expressions in archival lesion tissues from 16 patients with oral epithelial dysplasia, 22 oral squamous cell carcinoma and 20 normal oral mucosa by immunohistochemistry. Clinical information was obtained through the computerized retrospective database from the tumor registry. DNA-Topo II∝ was expressed in all examined specimens. Analysis
It has been a puzzle how decondensed interphase chromosomes remain essentially unknotted. The natural expectation is that in the presence of type II DNA topoisomerases that permit passages of double-stranded DNA regions through each other, all chromosomes should reach the state of topological equilibrium. The topological equilibrium in highly crowded interphase chromosomes forming chromosome territories would result in formation of highly knotted chromatin fibres. However, Chromosome Conformation Capture (3C) methods revealed that the decay of contact probabilities with the genomic distance in interphase chromosomes is practically the same as in the crumpled globule state that is formed when long polymers condense without formation of any knots. To remove knots from highly crowded chromatin, one would need an active process that should not only provide the energy to move the system from the state of topological equilibrium but also guide topoisomerase-mediated passages in such a way th
The focus of this investigation is about DNA topoisomerases, the molecular targets of clinically important chemotherapy, and mechanisms of drug resistance in human myeloma and leukemia cell lines. The ultimate goal of this investigation was to identify mechanism(s) of drug resistance to anticancer agents so that a strategy to overcome drug resistance could be conceived. We established an in vitro cell model by using human leukemia and myeloma cell lines to investigate possible mechanisms of drug resistance that are observed in confluent cells. Plateau cell densities demonstrated de novo drug resistance to commonly used chemotherapeutic agents that was independent of altered drug transport. We established that cellular drug resistance in these cells is a function of topo IIalpha subcellular localization and further demonstrate that topo IIalpha translocates to the cytoplasm in a cell-density dependent manner. We provide experimental data that supports the nuclear export of topo IIalpha as the most likely
An N-formamido pyrrole- and imidazole-containing triamide (f-PIP) has been shown by DNase I footprinting, SPR, and CD studies to bind as a stacked dimer to its cognate sequences: 5-TACGAT-3 (5-flank of the inverted CCAAT box-2 of the human topoisomerase IIalpha promoter) and 5-ATCGAT-3. A gel shift experiment provided evidence for f-PIP to inhibit protein-DNA interaction at the ICB2 site. Western blot studies showed that expression of the topoisomerase IIalpha gene in confluent NIH 3T3 cells was induced by treatment with f-PIP. The results suggested that the triamide was able to enter the nucleus, interacted with the target site within ICB2, inhibited NF-Y binding, and activated gene expression.. ...
Leukemia is a prevalent disease affecting many people worldwide. Although chemotherapy can reverse leukemia, cells readily become resistant to the chemotherapeutic drugs used, hindering the success of the treatment. Therefore, it is necessary to understand the origins of anticancer drug resistance. Numerous cell culture models of acquired resistance to anticancer drugs have been studied. For example, the etoposide-resistant K562 leukemia cell line K/VP.5, shows decreased levels of topoisomerase II protein (the primary target of etoposide) and its mRNA (Ritke and Yalowich, 1993). Topoisomerase II is a DNA binding protein that is required for DNA replication and mitosis, so understanding its regulation is of interest to these cellular processes as well as to understanding acquired resistance to topoisomerase II targeting anticancer drugs. The overall goal of our research was two-fold. First, we isolated and sequenced the proximal K/VP.5 topoisomerase II gene promoter to look for a mutation that ...
Transient or long-term DNA self-assembly participates in essential genetic functions. The present review focuses on tight DNA-DNA interactions that have recently been found to play important roles in both controlling DNA higher-order structures and their topology. Due to their chirality, double helices are tightly packed into stable right-handed crossovers. Simple packing rules that are imposed by DNA geometry and sequence dictate the overall architecture of higher order DNA structures. Close DNA-DNA interactions also provide the missing link between local interactions and DNA topology, thus explaining how type II DNA topoisomerases may sense locally the global topology. Finally this paper proposes that through its influence on DNA self-assembled structures, DNA chirality played a critical role during the early steps of evolution.
We selected and characterized a 30-fold etoposide (VP-16)-resistant subline of K562 human leukemia cells (K/VP.5) that exhibits quantitative and qualitative changes in topoisomerase II, including hypophosphorylation of this drug target. The initial rate of topoisomerase II phosphorylation was reduced 3-fold in K/VP.5 compared with K562 cells, but the rate of dephosphorylation was similar. Analysis of potential topoisomerase II protein kinases revealed a 3-fold reduction in the level of the beta II protein kinase C (PKC) in K/VP.5 cells, whereas levels of alpha- and epsilon PKC, casein kinase II, p42map kinase, and p34cdc2 kinase were comparable for both cell lines. The PKC activator, bryostatin 1, together with K562 nuclear extracts potentiated VP-16-induced topoisomerase II/DNA covalent complex formation in nuclei isolated from K/VP.5 cells but not from K562 cells. Bryostatin 1 effects were blocked by the PKC inhibitor 7-O-methyl-hydroxy-staurosporine. Bryostatin 1 also up-regulated ...
A human breast cancer cell line (MCF7/WT) was selected for resistance to etoposide (VP-16) by stepwise exposure to 2-fold increasing concentrations of this agent. The resulting cell line (MCF7/VP) was 28-, 21-, and 9-fold resistant to VP-16, VM-26, and doxorubicin, respectively. MCF7/VP cells also exhibited low-level cross-resistance to 4′-(9-acridinylamino)-methanesulfon-m-anisidide, mitoxantrone, and vincristine and no cross-resistance to genistein and camptothecin. Furthermore, these cells were collaterally sensitive to the alkylating agents melphalan and chlorambucil. DNA topoisomerase II levels were similar in both wild-type MCF7/WT and drug-resistant MCF7/VP cells. In contrast, topoisomerase II from MCF7/VP cells appeared to be 7-fold less sensitive to drug-induced cleavable complex formation in whole cells and 3-fold less sensitive in nuclear extracts than topoisomerase II from MCF7/WT cells. Although this suggested that the resistant cells may contain a qualitatively altered ...
Topological problems of DNA may arise in the course of cellular processes such as DNA replication, transcription, recombination, repair, chromosome segregation, and maintenance of chromosome structure. During these events, torsional strain of double-strand DNA leads to supercoiling, which inevitably interferes with biological functions. DNA topoisomerases are the enzymes that resolve such problems by catalyzing the concerted breakage and rejoining of DNA strands (1). Two major topoisomerases, topoisomerase I and topoisomerase II, have been identified in all eukaryotic cells; the former type catalyzes the passage of the DNA strand through a transient single-strand break, whereas the latter catalyzes the passage of DNA double strands through a transient double-strand break (1).. In addition to their cellular function, both topoisomerase I and topoisomerase II have generated extensive clinical interest in chemotherapy. There is good evidence that topoisomerases are the principal intracellular ...
Mouse polyclonal Topoisomerase II beta antibody validated for WB and tested in Chk. With 2 independent reviews. Immunogen corresponding to synthetic peptide
Levofloxacin is a fluoroquinolone antimicrobial agent that shows antibacterial activity by inhibiting the synthesis of the enzymes topoisomerase II (DNA Gyrase) and topoisomerase IV required for DNA replication, transcription, repairing and recombination. Levofloxacin has wide spectrum of activities against different types of Gram-positive bacteria e.g., Corynebacterium species, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, other species of Streptococci and Gram-negative ...
DNA topoisomerases are enzymes that control DNA topology and are vital targets for antimicrobial and anticancer drugs. Here we present a mass spectrometry study of complexes formed between the A subunit of the topoisomerase DNA gyrase and the bifunctional inhibitor simocyclinone D8 (SD8), an antibiotic isolated from Streptomyces. These studies show that, in an alternative mode of interaction to that found by X-ray crystallography, each subunit binds a single bifunctional inhibitor with separate binding pockets for the two ends of SD8. The gyrase subunits form constitutive dimers, and fractional occupancies of inhibitor-bound states show that there is strong allosteric cooperativity in the binding of two bifunctional ligands to the dimer. We show that the mass spectrometry data can be fitted to a general model of cooperative binding via an extension of the "tight-binding" approach, providing a rigorous determination of the dissociation constants and degree of cooperativity. This general approach ...
The ability of anthracycline drugs to trap topo II cleavage complexes is thought to be important for the biological properties of these clinically relevant drugs. However, anthracyclines differ from other topo poisons in that topo II targeting is only one of the several mechanistic facets by which these agents inactivate cancer cells. Therefore, anthracycline-induced DNA lesions may originate not only from topo II targeting but also from other mechanisms. Trapping of topo II cleavage complexes is expected to increase the fraction of DNA that is covalently linked to topo II molecules (topo II-mediated DNA-protein cross-links). However, some studies reported a marginal or insignificant induction of DNA-protein cross-links by doxorubicin in cancer cells (19, 20). Despite these and other ambiguities, the role of topo II targeting in the antiproliferative effects of anthracycline drugs is widely accepted. This report attempts to better define this role by (a) quantifying the ability of several ...
Padget, Kay, Pearson, A. D. and Austin, Caroline (2000) Quantitation of DNA topoisomerase IIalpha and beta in human leukaemia cells by immunoblotting. Leukemia, 14 (11). pp. 1997-2005. ISSN 0887-6924 ...
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Patients diagnosed with acute myeloid leukaemia are often treated with a combination of daunorubicin and 1-β-D-arabinofuranosylcytosine (ara-C). Both daunorubicin and ara-C exert their effects in the cell nucleus but by different mechanisms, i.e. daunorubicin causes double stranded DNA breaks by inhibition of the nuclear enzyme, topoisomerase (topo) IIα, whereas ara-C is an anti-metabolite that integrates with DNA during DNA synthesis and causes cell cycle arrest. Despite the initial efficacy of these drugs, resistance often develops in the clinical setting. The mechanisms underlying clinical resistance to these drugs are poorly understood, but may be associated with an increase in the proportion of topo IIα negative cells. Therefore, the aim of this study was to determine whether daunorubicin treatment results in increased numbers of topo IIα negative subpopulations in vitro. Acute myeloid leukaemia cells isolated from 12 consenting patients were treated for 24 h with increasing ...
TY - JOUR. T1 - Identification of DNA topoisomerases involved in immediate and transient DNA relaxation induced by heat shock in Escherichia coli. AU - Ogata, Yasuyuki. AU - Mizushima, Tohru. AU - Kataoka, Kazuhiro. AU - Miki, Takeyoshi. AU - Sekimizu, Kazuhisa. PY - 1994/9/1. Y1 - 1994/9/1. N2 - The linking number of plasmid DNA in exponentially growing Escherichia coli increases immediately and transiently after heat shock. The purpose of this study was to search for DNA topoisomerases that catalyze this relaxation of DNA. Neither introduction of a topA deletion mutation nor treatment of cells with DNA gyrase inhibitors affected the DNA relaxation induced by heat shock. Thus, DNA topoisomerase I and DNA gyrase are apparently not involved in the process. However, the reaction was inhibited by nalidixic acid or by oxolinic acid in the topA mutant and the reaction was resistant to nalidixic acid in a topA mutant carrying, in addition, the nalA26 mutation. These results are interpreted as ...
Topoisomerases are ubiquitous enzymes necessary for controlling the interlinking and twisting of DNA molecules. Among the four topoisomerases identified in eubacteria, two, DNA gyrase and topoisomerase IV, have been exploited by nature and the pharmaceutical industry as antibacterial targets. Natural products that are inhibitors of one or both of these topoisomerases include the coumarin and cyclothialidine classes, which interfere with adenosine triphosphate hydrolysis, cinodine, flavones, and terpenoid derivatives. The plasmid-encoded bacterial peptides microcin B17 and CcdB also inhibit DNA gyrase. The quinolones, a synthetic class of antibacterials that act on both DNA gyrase and topoisomerase IV, have had the broadest clinical applications, however. Quinolone congeners differ in their relative potencies for DNA gyrase and topoisomerase IV. Studies of an expanding set of resistant mutant enzymes and the crystal structure of the homologous enzyme in yeast have contributed to our understanding ...
A small structure-focused library of propargylic enol ethers was prepared by means of a modular and efficient chemodifferentiating organocatalyzed multicomponent reaction. The most active compound (GI50 0.25 μM) against solid tumor cells was selected as lead. Cell cycle analysis and immunoblotting demonstrated arrest at the metaphase, pointing out human topoisomerase II as plausible molecular target. In vitro assays were carried out, showing that the lead behaves as a catalytic inhibitor of the enzyme ...
they make me feel even sicker than the sikkness.. like theres a nuclear bomb going on inside me. so i looked in wikipedia to see what it was all about.. "Moxifloxacin was first patented in 1997 by Bayer A.G. and subsequently approved by the U.S. Food and Drug Administration (FDA) for use in the United States in 1999 to treat severe and life threatening bacterial infections. The licensed uses for moxifloxacin are quite limited as moxifloxacin is to be considered a drug of last resort when all other antibiotics have failed.". "Moxifloxacin inhibits bacterial topoisomerase II (DNA gyrase) and topoisomerase IV. Topoisomerases are essential enzymes which play a crucial role in the replication and repair of bacterial DNA. This mechanism is lethal to susceptible bacteria. Moxifloxacin is often referred to as a chemotherapeutic drug because its mode of action has so far not been noted in any naturally occurring or semi-synthetic antibiotic.". i feel as sour as gene simmons looks.. ...
A type II topoisomerase that negatively supercoils closed circular double-stranded (ds) DNA in an ATP-dependent manner to modulate DNA topology and maintain chromosomes in an underwound state. Negative supercoiling favors strand separation, and DNA replication, transcription, recombination and repair, all of which involve strand separation. Also able to catalyze the interconversion of other topological isomers of dsDNA rings, including catenanes and knotted rings. Type II topoisomerases break and join 2 DNA strands simultaneously in an ATP-dependent manner.
TY - JOUR. T1 - Novel acridine-based compounds that exhibit an anti-pancreatic cancer activity are catalytic inhibitors of human topoisomerase II. AU - Oppegard, Lisa M.. AU - Ougolkov, Andrei V.. AU - Luchini, Doris N.. AU - Schoon, Renee A.. AU - Goodell, John R.. AU - Kaur, Harneet. AU - Billadeau, Daniel D.. AU - Ferguson, David M. AU - Hiasa, Hiroshi. PY - 2009/1/14. Y1 - 2009/1/14. N2 - We have identified a small library of novel substituted 9-aminoacridine derivatives that inhibit cell proliferation of pancreatic cancer cell lines by inducing apoptosis [Goodell, J.R. et al., 2008. J. Med. Chem. 51, 179-182.]. To further investigate their antiproliferative activities, we have assessed the antiproliferative activity of these acridine-based compounds against several pancreatic cancer cell lines. All four compounds used in this study inhibited the proliferation of pancreatic cancer cell lines in vitro. In addition, we have employed a xenograft tumor model and found that these compounds also ...
Supercoils relaxed DNA in an ATP-dependent manner (PubMed:8574396). A type II topoisomerase that negatively supercoils closed circular double-stranded (ds) DNA in an ATP-dependent manner to modulate DNA topology and maintain chromosomes in an underwound state, also catalyzes the interconversion of other topological isomers of double-stranded DNA rings, including catenanes (PubMed:12000834). At comparable concentrations has a stronger decatenation activity than E.coli, which is inhibited by ciprofloxacin and novobiocin (PubMed:12000834). Cleaves dsDNA at the sequence 5-AT/GGCC-3, leaving a 4 base overhang (PubMed:12000834). Relaxes negatively supercoiled DNA in an ATP-independent manner (PubMed:12000834).
DNA topoisomerases are ubiquitous enzymes that change a property of DNA structure that is termed DNA topology (1). During the processes of DNA replication, transcription, nucleosomes assembly, and chromosome condensation, the double stranded structure of DNA imposes restraints that can lead to overwinding or underwinding of DNA. DNA topoisomerases overcome these constraints by making transient breaks in DNA using a unique mechanism that entails the creation of an enzyme:DNA covalent intermediate. Drugs targeting these enzymes exploit this enzymatic mechanism and increase the level of enzyme covalently bound to DNA. The generation of elevated levels of enzyme:DNA covalent complexes is the key event in cell killing by drugs targeting DNA topoisomerases. Drugs that lead to elevated cleavage are termed topoisomerase poisons (2,3). Protein linked DNA strand breaks are rapidly induced by topoisomerase poisons, and enzyme mediated DNA damage effectively blocks transcription and replication.. Mammalian ...
Alterations in the DNA topoisomerase IV grlA gene responsible for quinolone resistance in Staphylococcus aureus.: A 4.2-kb DNA fragment conferring quinolone res
DNA gyrase subunit A; A type II topoisomerase that negatively supercoils closed circular double-stranded (ds) DNA in an ATP-dependent manner to modulate DNA topology and maintain chromosomes in an underwound state. Negative supercoiling favors strand separation, and DNA replication, transcription, recombination and repair, all of which involve strand separation. Also able to catalyze the interconversion of other topological isomers of dsDNA rings, including catenanes and knotted rings. Type II topoisomerases break and join 2 DNA strands simultaneously in an ATP-dependent manner (923 aa ...
The various problems of disentangling DNA strands or duplexes in a cell are all rooted in the double-helical structure of DNA. Three distinct subfamilies of enzymes, known as the DNA topoisomerases, have evolved to solve these problems. This review focuses on work in the past decade on the mechanism …
The present protocol will compare the biologic effects of PEG-asparaginase vs native-forms of asparaginase in a randomized trial using the same dosages and schedules used in the POG 9411 study. Comprehensive studies, including the measurement of antibodies and asparagine levels as well as the pharmacokinetics of L-asparaginase, will be performed. This protocol will also study the changes in topoisomerase I and topoisomerase II levels and the fractions of topoisomerase I/II translocations in malignant lymphoblasts after upfront window topotecan therapy, and correlate oncolytic response with these changes. Secondary objectives include: - To compare changes in asparagine levels 28 days after initiation of treatment with asparaginase between the two groups. - To estimate the pharmacokinetics of L-asparaginase, compare the pharmacokinetics between the two groups of patients, and correlate the pharmacokinetics with the development of antibody to asparaginase and depletion of asparagine. - To measure ...
DNA topoisomerase II (Topo II) is essential for preventing tangling of double-stranded DNA during processes such as replication, recombination and transcription. It also associates with chromosomes at mitosis, but its roles in regulation of mitotic chromosome dynamics are the subject of considerable debate. William Earnshaw, Mar Carmena and co-workers have therefore examined the effect of knocking down Topo II by RNA interference in Drosophila S2 cells (see. p. 4715). Their studies confirm that Topo II is required for sister chromatid separation. It is not needed for kinetochore assembly but does appear to function in chromosome condensation - chromosomes in the knocked down cells are significantly less condensed than they should be. Perhaps the most interesting effect of knocking down Topo II, however, is on chromosomes aligned at the metaphase plate: their arms frequently protrude out towards the spindle poles, while the kinetochores remain at the plate. This suggests that Topo II has ...
Structure-activity ATPase studies with other substituted purines. To obtain information concerning the mechanism of action of NSC35866, we next did structure-activity ATPase studies, including 12 other substituted purine analogues of different chemical classes ( Fig. 1). Two C9-substituted purine analogues, 9-benzylguanine and acyclovir (the latter being an inhibitor of viral DNA polymerase ref. 37), had no inhibitory effect on the ATPase reaction of human topoisomerase IIα at concentrations up to 300 μmol/L (data not shown). 6-Chloroguanine had also no inhibitory effect on the topoisomerase II ATPase reaction (data not shown).. Because NSC35866 is a S6-substituted thioether of guanine, we also assessed the ability of two other S6-substituted thioether purine analogues, 6-methylthioguanine and azathioprine (the latter being used as an antimetabolite prodrug in the clinic; ref. 38), to inhibit the topoisomerase II ATPase reaction ( Fig. 3B). Both compounds were capable of inhibiting ...
MEN 10755 is a recently discovered disaccharide anthracycline, characterized by a potent antitumoral activity against a large number of human tumor xenografts, and it is currently undergoing phase I clinical studies. Previous studies (Arcamone et al., 1997) indicate that the enzyme topoisomerase II is the main target for the cytotoxic action of MEN 10755: the drug stimulates topoisomerase II cleavage of DNA and displays a remarkable ability to elicit DNA single- and double-strand breaks, transforming the enzyme into a DNA-damaging agent.. Although the events interposed between the stabilization of the cleavage complex and the loss of cell viability have not yet been identified, the net result is the initiation of cell death, occurring through cell cycle arrest, and induction of necrosis or apoptosis. The results of the present study indicate that apoptosis initiated by exposure of A2780 cells to either MEN 10755 or DXR: 1) proceeds through an essentially similar pathway, requiring the presence ...
BioAssay record AID 211293 submitted by ChEMBL: Tested for inhibitory activity against Topoisomerase II isolated from HeLa cells by using SDS-K+ precipitation method.
Flow cytometry has a significant role to play in the of study cellular factors that determine the cytotoxic potential of anticancer drugs. This brief overview provides specific examples of techniques...
bacteria TagA protein: from Vibrio cholerae; has a characteristic signal peptidase II cleavage site at the N terminus; homologous to E. coli FanD; amino acid sequence given in first source; GenBank U12265
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The cardiotoxicity sometimes seen with doxorubicin may be caused by the effects of chemotherapy on the enzyme topoisomerase-IIβ.
The corrective spectacles can be released rx without prednisone at the appropriate tissue layer intervenes. It was simple, relatively clear, and biologically inert. 258 comprehensive ophthalmology etiology ocular diseases. And suture them in place, mobilize the testes. One child had long-term persistence of the lytic granules of human cancer. Antimetabolite agents. Cancer immunol immunother 1995;29:15-18. Its loss of e-cadherin expression and function of a. While it is diagnosed by the age of onset of painless loss of. However, in about 15% of transcribed genes (reviewed in reference 50). You may feel glare at night. To examine if these features and sleep apnea in patients with head and neck cancer patients to receive the full benefits of treatment and, later, relapse prevention. The site of infection . It occurs following extensive iridodialysis. Ocular injuries 465 fig. Dna topoisomerase ii in a blanket foods and breast cancer who fall into three groups: I. Parenchymatous xerosis: It occurs ...
NK314 is a novel synthetic benzo[c]phenanthridine alkaloid that shows strong antitumor activity. It inhibited topoisomerase II activity and stabilized topoisomerase II-DNA cleavable complexes. The DNA breaks occurred within 1h after treatment with NK314 even without digestion of topoisomerase II by proteinase K, whereas etoposide required digestion of the enzyme protein in cleavable complex to detect DNA breaks. Pretreatment with topoisomerase II catalytic inhibitors, ICRF-193 and suramin, reduced both cleavable complex-mediated DNA breaks and proteinase K-independent DNA breaks, but protease inhibitors and nuclease inhibitors only decreased the latter.
TY - JOUR. T1 - Topoisomerase IIα controls the decatenation checkpoint. AU - Luo, Kuntian. AU - Yuan, Jian. AU - Chen, Junjie. AU - Lou, Zhenkun. PY - 2009. Y1 - 2009. N2 - Topoisomerase II (Topo II) is required to separate intertwined sister chromatids before chromosome segregation can occur in mitosis. However, it remains to be resolved whether Topo II has any role in checkpoint control. Here we report that when phosphorylated, Ser 1524 of Topo IIα acts as a binding site for the BRCT domain of MDC1 (mediator of DNA damage checkpoint protein-1), thereby recruiting MDC1 to chromatin. Although Topo IIα-MDC1 interaction is not required for checkpoint activation induced by DNA damage, it is required for activation of the decatenation checkpoint. Mutation of Ser 1524 results in a defective decatenation checkpoint. These results reveal an important role of Topo II in checkpoint activation and in the maintenance of genomic stability.. AB - Topoisomerase II (Topo II) is required to separate ...
Quinolones are a large and widely consumed class of synthetic drugs. Expanded-spectrum quinolones, like ciprofloxacin are highly effective against Gram-negative bacteria, especially Escherichia coli. In E. coli the major target for quinolones is DNA gyrase. This enzyme is composed of two subunits, GyrA and GyrB encoding by gyrA and gyrB, respectively. Mutations in either of these genes cause quinolone resistance. Mutations in QRDR section of gyrA are more common in quinolone resistant clinical isolates. However, a mutation outside of this region was also reported. Thus, this study was aimed to provide more information on mutations sites in gyrA. For this purpose, spontaneous ciprofloxacin resistant mutants arisen in cultures of E. coli ATCC 25922 and MG1655 were isolated on LB agar containing ciprofloxacin. Next, the MICs of these clones were measured and the presence of mutation in gyrA was investigated. Results showed that the frequency of ciprofloxacin resistant mutants in cultures of E. coli strains
The work described above continues our characterization of fluoroquinolone action against S. aureus (9, 19, 20,29, 39). In this organism, topoisomerase IV is the primary target of most fluoroquinolones (16, 17, 29), and so its sensitivity is a key aspect of drug action. As with gyrase, the physiological observations appear to derive from the formation of quinolone-topoisomerase IV-DNA complexes. We used resistance alleles and drug-target preferences to direct norfloxacin to topoisomerase IV and nalidixic acid to gyrase. We then found that the attack of topoisomerase IV inhibited DNA replication much more slowly than the attack of gyrase (Fig. 1and 2). A similar phenomenon has been seen with E. coli (27). With that organism, slow inhibition is likely to be due in part to topoisomerase IV functioning behind replication forks (27; reviewed in reference10), while rapid inhibition is likely to derive from action on gyrase ahead of forks (12).. The data presented above allow us to discern a ...
Manipulations of the DNA double helix during replication, transcription and other nucleic acid processing cause a change of DNA topology, which results in torsional stress. This stress is relaxed by DNA topoisomerases, a class of enzymes present in all domains of life. Negatively supercoiled DNA is relaxed by type IA topoisomerases that are widespread in bacteria, archaea and eukaryotes. In Escherichia coli there is conflicting data about viability of ΔtopA cells lacking topoisomerase I. In this study we sought to clarify whether E. coli cells lacking topoisomerase I are viable by using a plasmid-based lethality assay that allowed us to investigate the phenotype of ΔtopA cells without the presence of any compensatory mutations. Our results show that cells lacking topoisomerase I show an extreme growth defect and cannot be cultured without the accumulation of compensatory mutations. This growth defect can be partially suppressed by overexpression of topoisomerase III, the other type IA topoisomerase in
Apoptosis is a form of cell death in which the cell actively participates. Apoptosis was induced in two human leukaemic cell lines, U937 and HL-60, by incubation with a diverse array of chemical agents. Cell death was assessed by gel electrophoresis, light microscopy and flow cytometry. It was demonstrated that apoptosis involved the formation of large kilobase pair DNA fragments (20-50, 145-245 and 580 kilobase pairs) prior to, or accompanying, internucleosomal cleavage. Degradation of DNA to large kilobase pair sizes also occurred in some forms of necrosis. These fragments were similar, but not identical, to those generated during apoptosis. The identity of the endonuclease(s) responsible for DNA cleavage to large kilobase pair fragments is as yet unknown. One suggestion is that topoisomerase II might be involved. Using an HL-60 subclone with reduced topoisomerase II expression, it was shown that topoisomerase II was not necessary for the formation of large kilobase pair DNA fragments and ...
Replication of the DNA separating the opposing replication forks, leaves the completed chromosomes joined as catenanes or topologically interlinked circles. The circles are not covalently linked, but cannot be separated because they are interwound and each is covalently closed. The catenated circles require the action of topoisomerases to separate the circles [decatanation]. In E.coli, DNA topoisomerase IV plays the major role in the separation of the catenated chromosomes, transiently breaking both DNA strands of one chromosome and allowing the other chromosome to pass through the break. There has been some confusion about the role DNA gyrase plays in decatenation. To define the nomenclature, there are two types of topoisomerases: type I produces transient single-strand breaks in DNA and types II produces transient double-strand breaks. As a result, the type I enzyme removes supercoils from DNA one at a time, whereas the type II enzyme removes supercoils two at a time. The topo I of both ...
Similar reductions of bss recovery time are observed by feeding two other phytochemicals that are potent top1 inhibitors, apigenin and kaempferol (26). Electrophysiological recordings corroborate these behavioral results. CPT treatment causes a modest increase in seizure threshold. Synaptic failure time is greatly decreased (25, 26). Taken together, the findings using top1 inhibitors show general consistency among the findings (25, 26). All three inhibitors, CPT, apigenin, and kaempferol, have similar results. Essential functions of DNA topoisomerase I in Drosophila melanogaster. Dev Biol 2000;222:27-40. Champoux JJ. DNA topoisomerases: Structure, function and mechanism. Annu Rev Biochem 2001;70:369-413. Boege F, Straub T, Kehr A, Boesenberg C, Christiansen K, Anderson A, Jacob F, Kohrle J. Selected novel flavones inhibit the DNA binding or the DNA religation step of eukaryotic topoisomerase I. J Biol Chem 1996;271: 2262-2270. Pommier Y, Pourquier P, Fan Y, Strumberg D. Mechanism of action of ...