InhibitorTopo IIGyraseColiTopologyCamptothecinHuman topoisomeraseTOP1EtoposideInhibitors in clinicalInhibitionTopotecanInhibiting DNA replicationEukaryotesChromosomeCatalytic activityAntitumor activityChemical compoundsTop2aEnzymes calledSUMOylationTypeBreakageEnzyme ActivityTopoGENStrandMechanismsTargetsReplication and transcriptionMetastaticResistanceDrugsCancerActivityMoleculesHelixTopological stateCleavagePlasmidProteinsPossible involvementCell
Inhibitor9
- Zymeworks Topoisomerase-1 inhibitor technology uses a novel fit-for-purpose camptothecin payload with moderate potency and strong bystander activity in conjunction with a traceless, plasma-stable, cleavable peptide linker. (zymeworks.com)
- Catabolism of the ADC following target engagement, internalization, and lysosomal trafficking releases the topoisomerase inhibitor payload ZD06519. (zymeworks.com)
- We have shown that colorectal cancer cell lines defective in DNA MMR exhibit an increased sensitivity to both camptothecin, a topoisomerase I inhibitor, and etoposide, a topoisomerase II inhibitor. (aacrjournals.org)
- In this study, treatment of EMT6 mouse mammary tumor cells with hypoxia or the chemical stress agents brefeldin A (BFA) or okadaic acid (OA) causes the development of resistance to the topoisomerase II inhibitor etoposide. (aspetjournals.org)
- Camptothecin (CPT), a plant alkaloid with antitumor activity, is a specific inhibitor of eukaryotic DNA topoisomerase I. We have previously isolated and characterized a CPT-resistant topoisomerase I isolated from a CPT-resistant human leukemia cell line, CPT-K5. (duke.edu)
- Biological Activity： Topoisomerase I/II inhibitor 3 (compound 7) is a potent topoisomerase I (Topo I) and II (Topo II) dual inhibitor. (epigenetics-modulation-frontier.com)
- Topoisomerase I/II inhibitor 3 can inhibit cell proliferation, invasion and migration, and induce apoptosis by inhibiting PI3K/Akt/mTOR signaling pathway. (epigenetics-modulation-frontier.com)
- Topoisomerase I/II inhibitor 3 can be used for liver cancer research. (epigenetics-modulation-frontier.com)
- The ADCs sacituzumab govitecan (Trodelvy) and trastuzumab deruxtecan (Enhertu), for instance, both incorporate a topoisomerase inhibitor as their toxic payload. (medscape.com)
Topo II3
- Our group has identified DNA topoisomerase IIα (Topo IIα) as one of the important mitotic proteins for SUMOylation. (ku.edu)
- Tumor cell resistance to anthracyclines and epipodophyllotoxins can be due to reduced drug accumulation and/or alterations in the activity of topoisomerase II (TOPO II). (ucy.ac.cy)
- The effects of WR-1065 (2-((aminopropyl)amino)ethanethiol) on cell cycle progression, topoisomerase (topo) IIα activity, and topo IIα phosphorylation in Chinese hamster ovary (CHO) cells have been investigated. (ucy.ac.cy)
Gyrase7
- The first type II topoisomerase to be discovered was DNA gyrase from bacteria, by Martin Gellert and coworkers in 1976, and also characterized by Nicholas Cozzarelli and co-workers. (wikipedia.org)
- The exception among the type I topoisomerases, reverse gyrase, which contains a helicase domain (EC 3.6.4.12) and introduces positive supercoiling in an ATP-dependent manner. (wikipedia.org)
- With the exception of reverse gyrase, this unique type IA topoisomerase does require ATP and generates positive DNA supercoils rather than unwinding them. (jove.com)
- The only enzyme that introduces the positive supercoiling in DNA is a reverse gyrase enzyme, which is coupled with a helicase found in archaea and is a type IA topoisomerase. (excedr.com)
- There are three types: type IIa (examples are DNA gyrase, topoisomerase IV, and human topoisomerase IIɑ and II𝛃), Type IIb, and Type IIC. (excedr.com)
- The targets of quinolone activity are the bacterial DNA gyrase and topoisomerase IV, enzymes essential for DNA replication and transcription. (cdc.gov)
- DNA gyrase and topoisomerase IV. (cdc.gov)
Coli5
- it is now called Escherichia coli (E. coli) topoisomerase I (topo I) and is a representative of the type IA family of enzymes. (wikipedia.org)
- In the case of Escherichia coli DNA topoisomerase I, it has been suggested that a 30 kDa fragment moves away from the rest of the protein to create an entrance into the central hole in the protein. (rcsb.org)
- Topoisomerase was discovered in 1957 by the scientist J.C. Wang when he was working on Escherichia coli (or E.coli). (excedr.com)
- Bakterielle DNA-Topoisomerase I was expressed and purified from E. coli. (proteros.com)
- DNA topo III is a type IA topoisomerase that is similar to the prokaryotic (E. coli) topo I (omega protein). (topogen.com)
Topology3
- The book should appeal to readers from undergraduates upwards with interests in the biological and clinical aspects of topoisomerase function, or in the mathematics and physics of topology. (cshlpress.com)
- DNA topoisomerases, ubiquitously present in eukaryotes, archaebacteria and Eubacteria, are necessary for the regulation of DNA topology in various cellular procedures [ 3 , 4 ]. (jcancer.org)
- The modulation of DNA topology by topoisomerase II plays a crucial role during chromosome condensation and segregation in mitosis and has thus become a highly attractive target for chemotherapeutic drugs. (uea.ac.uk)
Camptothecin4
- Camptothecin analogs as potent inhibitors of topoisomerase I . (U.S. Patent No. 5106742 ). (rti.org)
- The camptothecin analogs are effective inhibitors of topoisomerase I and show anti-leukemic and anti-tumor activity. (rti.org)
- S)-10-Hydroxycamptothecin is a camptothecin derivative that inhibits DNA topoisomerase by enacting strand breaks in chromosomal DNA and inducing apoptosis. (adooq.com)
- Scholars@Duke publication: Molecular cloning of a cDNA of a camptothecin-resistant human DNA topoisomerase I and identification of mutation sites. (duke.edu)
Human topoisomerase3
- Background Genetic alterations in human topoisomerase II alpha (TOP2A) are linked to cancer susceptibility. (whiterose.ac.uk)
- High purity, catalytically active Human Topoisomerase I Enzyme over-expressed in the baculovirus system and purified to single band homogeneity. (topogen.com)
- Human Topoisomerase I enzyme is shipped on dry ice and should be stored at -20°C. It has a life-time of about 6 months when stored under optimal conditions. (topogen.com)
TOP12
- Here, the rolling circle amplification method, termed rolling circle enhanced enzyme activity detection (REEAD) assay that allows for the quantitative measurement of topoisomerase 1 (TOP1) activity in a simple, fast, and gel-free manner is presented.By cleaving and ligating a specially designed DNA substrate, TOP1 converts a DNA oligonucleotide into a closed circle, which becomes the template for rolling circle amplification, yielding ~103 tandem repeat rolling circle products. (au.dk)
- DNA Topoisomerase I (Top1) is often thought to regulate R-loop formation owing to its ability to resolve both positive and negative supercoils. (escholarship.org)
Etoposide1
Inhibitors in clinical2
- Furthermore, they imply that coadministration of agents that inhibit NF-κB may enhance the efficacy of topoisomerase II inhibitors in clinical cancer chemotherapy. (aspetjournals.org)
- CPT-11 and Topotecan are two potent DNA topoisomerase I inhibitors in clinical. (immune-system-research.com)
Inhibition1
- Inhibition or poisoning of maternal topoisomerase II delays embryonic development by extending the cell cycle M-phase. (whiterose.ac.uk)
Topotecan1
- Topotecan inhibits topoisomerase I, inhibiting DNA replication. (medscape.com)
Inhibiting DNA replication1
- SN-38 binds to and stabilizes the topoisomerase I-DNA complex and prevents the relegation of DNA after it has been cleaved by topoisomerase I, inhibiting DNA replication. (medscape.com)
Eukaryotes2
- Type II topoisomerases were subsequently identified from bacterial viruses and eukaryotes. (wikipedia.org)
- In all eukaryotes, topoisomerases are the key DNA-binding enzymes involved in the control of the DNA topological state during important cellular processes and are among the important biomarkers for cancer prognosis and treatment. (au.dk)
Chromosome4
- This book, written by James Wang, the discoverer of the first topoisomerase and a leader in the field since, presents ten chapters covering the historical backdrop of the DNA entanglement problem and the discovery of the DNA topoisomerases, how DNA topoisomerases perform their magic in DNA replication, transcription, genetic recombination and chromosome condensation, and how they are targets of therapeutic agents. (cshlpress.com)
- Topoisomerases are nuclear enzymes that modify the topological state of DNA and participate in fundamental metabolic processes such as replication, transcription, repair, recombination, and chromosome segregation (1) . (aacrjournals.org)
- TOP2A (DNA topoisomerase II alpha) gene, mapped to chromosome 17q12-q21, covers approximately 27.5 kb and includes 35 exons, encoding a 170 kDa protein [ 7 ]. (jcancer.org)
- In mitosis, chromosome condensation is controlled by another SMC complex, condensin, and the type II topoisomerase (Top2). (figshare.com)
Catalytic activity2
- TOP2A is one of the isoenzymes which can mediate the catalytic activity of type II topoisomerases [ 6 ]. (jcancer.org)
- Selected flavonoids were tested for their ability to inhibit the catalytic activity of DNA topoisomerase (topo) I and II. (ucy.ac.cy)
Antitumor activity1
- Six of the interacting proteins were cellular chaperones, including 3 members of the heat shock protein-90 (Hsp90) family, and so the effect of Hsp90 modulation on the antitumor activity of topoisomerase II drugs was tested using the sulforhodamine B assay, clonogenic assays and a xenograft model. (uea.ac.uk)
Chemical compounds2
- Some chemical compounds can inhibit the functional roles of topoisomerases in organisms. (excedr.com)
- Topoisomerase inhibitors are chemical compounds that block the action of topoisomerases . (github.io)
Top2a1
- Topoisomerase II alpha is also required for embryonic development in mammals, as mouse Top2a knockouts result in embryonic lethality as early as the 4-8 cell stage. (whiterose.ac.uk)
Enzymes called2
- A group of enzymes called DNA topoisomerases solve this problem by breaking and rejoining DNA molecules in a controlled manner, thereby allowing strands to be passed through each other and thus untangled not just during DNA replication, but also during many other basic cellular processes. (cshlpress.com)
- Topoisomerase inhibitors block cancer cells from dividing and spreading by interfering with enzymes called topoisomerases. (healthline.com)
SUMOylation1
- Resolution of sister centromeres requires RanBP2-mediated SUMOylation of topoisomerase IIalpha. (bvsalud.org)
Type12
- They do this by binding to DNA and cutting the sugar-phosphate backbone of either one (type I topoisomerases) or both (type II topoisomerases) of the DNA strands. (wikipedia.org)
- Therefore it is the sole type I topoisomerase classified as EC 5.6.2.2 (Table 1). (wikipedia.org)
- Type I topoisomerases are ATP-independent and act by cutting a bond between nucleotides on a single strand of double stranded DNA. (jove.com)
- Type II topoisomerases, on the other hand, are ATP-dependent and act on supercoiled DNA where the DNA is tangled around itself. (jove.com)
- Then, using the energy from a second ATP, Type II topoisomerase reseals the broken ends of the DNA strands and finally detaches from the DNA- leaving behind an untangled DNA helix. (jove.com)
- Type I Topoisomerases act on one strand of double-stranded DNA, and they are further divided into three categories: IA, IB, and IC. (jove.com)
- Most Type I topoisomerases do not require ATP to relax supercoiled DNA. (jove.com)
- Bacteria possess two closely related yet functionally distinct essential type IIA topoisomerases (Topos). (rcsb.org)
- In a rapid purification procedure, two distinct type II topoisomerase activities (decatenation and catenation) have been isolated from the whole cell extracts of Trypanosoma brucei brucei. (eurekaselect.com)
- According to their different acting mechanisms, DNA topoisomerases can be classified as type I and type II enzymes [ 3 , 6 ]. (jcancer.org)
- In type II topoisomerases, ATPases are located either on the N-terminus (type IIA) or the B subunit (type IIB). (excedr.com)
- An illustration of the working mechanism of type I topoisomerase. (excedr.com)
Breakage1
- It acts throughout the entire cell cycle and by direct intercalating into DNA triggers DNA breakage by topoisomerase II, causing subsequent cytocydal activity. (medscape.com)
Enzyme Activity1
TopoGEN1
- Recombinant Human Topo I Enzyme for use in all Topoisomerase I Kits from TopoGEN. (topogen.com)
Strand3
- They work by binding to topoisomerase and causing single-strand DNA breaks. (medscape.com)
- Also known as DNA topoisomerase I. This enzyme cuts the single strand of the DNA double helix and does not require ATP to perform the DNA cleavage. (excedr.com)
- The uncut DNA strand passes through the DNA break, and at this position, topoisomerase changes its conformation from a closed to an open state. (excedr.com)
Mechanisms1
- Different types of topoisomerases have different action mechanisms based on their structure. (excedr.com)
Targets3
- Because of their intimate involvement in the workings of the cell, topoisomerases are also the logical targets of many antibiotics (including Cipro) and anticancer agents. (cshlpress.com)
- A pair of 5'TCCTT3' topoisomerase recognition sites, 90 bp 5' of the inverted repeat axis, and near the base of the extruded cruciform, were identified which may be the topoisomerase resolution targets. (uoguelph.ca)
- We suggest that this resolution event involves free branch migration of the cruciform base (Holliday junction) towards the 3' end of resolution targets, covalently-bound by topoisomerase. (uoguelph.ca)
Replication and transcription1
- Topoisomerases are enzymes that relax overwound DNA molecules during various cell processes, including DNA replication and transcription. (jove.com)
Metastatic1
- Epidermal growth factor-induced heparanase nucleolar localization augments DNA topoisomerase I activity in brain metastatic breast cancer. (topogen.com)
Resistance1
- The resistance index (greater than 125) of the CPT-K5 fusion topoisomerase I is similar to that of the native CPT-K5 topoisomerase I. These results indicate that either or both of the two amino acid changes identified in the mutant enzyme is responsible for the resistance to CPT. (duke.edu)
Drugs4
- Sensitivity to these drugs cannot be predicted by measuring endogenous levels of topoisomerase I and II. (aacrjournals.org)
- Over the years, topoisomerases have been substantially investigated as a potential target of antiparasitic and anticancer drugs with libraries of natural and synthetic small-molecule compounds that are investigated every year. (au.dk)
- Intercalating drugs block the reconnection step, freezing the topoisomerase after it has broken the DNA. (github.io)
- Drugs that fall in the subgroup called topoisomerase II inhibitors can increase your risk of developing a second cancer. (healthline.com)
Cancer2
- Our results also indicate that neither p53 status, nor cell cycle alterations correlate with the sensitivity of colorectal cancer cells to topoisomerase inhibitors. (aacrjournals.org)
- Ren L, Liu J, Gou K, Xing C. Copy number variation and high expression of DNA topoisomerase II alpha predict worse prognosis of cancer: a meta-analysis. (jcancer.org)
Activity1
- Similar topoisomerase activity was observed by James Champoux and Renato Dulbecco in eukaryotic cells. (excedr.com)
Molecules1
- However, the broken bonds in the DNA molecules reform as soon as the topoisomerase enzyme leaves the strands. (excedr.com)
Helix2
- In Untangling the Double Helix, Wang offers a very accessible and thorough introduction to DNA topoisomerases, from their basic properties to their roles in biology and medicine. (cshlpress.com)
- Another DNA double helix passes through the DNA breaks, and the topoisomerase enzyme changes its conformation, which requires ATP hydrolysis. (excedr.com)
Topological state1
- DNA topoisomerases (or topoisomerases) are enzymes that catalyze changes in the topological state of DNA, interconverting relaxed and supercoiled forms, linked (catenated) and unlinked species, and knotted and unknotted DNA. (wikipedia.org)
Cleavage1
- Doxorubicin and its derivatives inhibit the functions of the human topoisomerases by stabilizing the cleavage complex. (excedr.com)
Plasmid1
- Recombinant SFV topoisomerase resolution was shown to require plasmid substrates bearing inverted repeat telomeric concatemer junctions extruded as cruciforms. (uoguelph.ca)
Proteins4
- One such strategy is to target topoisomerase II-interacting proteins. (uea.ac.uk)
- Here we report the identification of potential topoisomerase II-associated proteins using immunoprecipitation, followed by 1-D and 2-D gel electrophoresis and MALDI-TOF mass spectrometry. (uea.ac.uk)
- A total of 23 proteins were identified and, of these, 17 were further validated as topoisomerase IIα-associated proteins by coimmunoprecipitation and Western blot. (uea.ac.uk)
- Thus, our method of identifying topoisomerase II-interacting proteins appears to be effective, and at least 1 novel topoisomerase IIα-associated protein, Hsp90, may represent a valid drug target in the context of topoisomerase II-directed chemotherapy. (uea.ac.uk)
Possible involvement1
- Because MMR is assumed to modulate cytotoxicity to various chemotherapeutic agents that act upon DNA, our objectives have been to define its possible involvement in the cytotoxicity of topoisomerase inhibitors. (aacrjournals.org)
Cell3
- Topoisomerase-inhibiting antineoplastic agents prevent cell growth and proliferation. (medscape.com)
- Topoisomerase inhibitors inhibit cell growth and proliferation. (medscape.com)
- cDNA clones of topoisomerase I were isolated from the CPT-resistant and the parental CPT-sensitive cell lines, respectively. (duke.edu)