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| topoisomerase ISummaryGene Symbol: topoisomerase I Description: topoisomerase (DNA) I Alias: TOPI, DNA topoisomerase 1, type I DNA topoisomerase Species: human Top Publications
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Publications
[Topotecan: a new field of use]S Ferrari
, Pavia
Tumori 85:S23-8. 1999..of the alkaloid camptothecin is an antitumor drug that like other camptothecin derivatives, targets DNA topoisomerase I, an enzyme that is present in cells in concentration relatively independent of the stage in the cell cycle...- Different distribution of HLA class II alleles in anti-topoisomerase I autoantibody responders between silicosis and systemic sclerosis patients, with a common distinct amino acid sequence in the HLA-DQB1 domainA Ueki
Department of Hygiene, Kawasaki Medical School, Kurashiki, Japan
Immunobiology 204:458-65. 2001Autoantibodies against DNA topoisomerase I (anti-topo I) have been reported to be specific to systemic sclerosis (SSc), however, anti-topo I was detected in patients with silicone breast implants, SLE without features of SSc, and .. 
The mechanism of topoisomerase I poisoning by a camptothecin analogBart L Staker
deCODE Genetics, Incorporated, BioStructures Group, 7869 Northeast Day Road West, Bainbridge Island, WA 98110, USA
Proc Natl Acad Sci U S A 99:15387-92. 2002We report the x-ray crystal structure of human topoisomerase I covalently joined to double-stranded DNA and bound to the clinically approved anticancer agent Topotecan...- Topoisomerase 1 and single-strand break repair modulate transcription-induced CAG repeat contraction in human cellsLeroy Hubert
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA
Mol Cell Biol 31:3105-12. 2011..These studies broaden the scope of pathways involved in transcription-induced CAG repeat instability and begin to define their interrelationships... - SUMO-1 conjugation to topoisomerase I: A possible repair response to topoisomerase-mediated DNA damageY Mao
Department of Pharmacology, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA
Proc Natl Acad Sci U S A 97:4046-51. 2000Ubiquitin/26S proteasome-dependent degradation of topoisomerase I (TOP1) has been suggested to be a unique repair response to TOP1-mediated DNA damage... - SUMO-1 conjugation to intact DNA topoisomerase I amplifies cleavable complex formation induced by camptothecinKoji Horie
Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo ku, Japan
Oncogene 21:7913-22. 2002DNA topoisomerase I (Topo1) manages the topological state of DNA. Cleavable complexes, the covalent Topo1-DNA intermediates, become DNA damaged when the catalytic cycles are inhibited by the anti-tumor drug camptothecin (CPT)... - The histone variant mH2A1.1 interferes with transcription by down-regulating PARP-1 enzymatic activityKhalid Ouararhni
Laboratoire Epigénétique et Cancer, Centre National de la Recherche Scientifique FRE 2944, 94801 Villejuif, France
Genes Dev 20:3324-36. 2006..mH2A1.1 recruits PARP-1 to the promoter, thereby inactivating it. Upon heat shock, the Hsp70.1 promoter-bound PARP-1 is released to activate transcription through ADP-ribosylation of other Hsp70.1 promoter-bound proteins... - Single mutation in the linker domain confers protein flexibility and camptothecin resistance to human topoisomerase IPaola Fiorani
Department of Biology, University of Padua, Via U Bassi 58 B, Padua 35131, Italy
J Biol Chem 278:43268-75. 2003DNA topoisomerase I relaxes supercoiled DNA by the formation of a covalent intermediate in which the active-site tyrosine is transiently bound to the cleaved DNA strand... - The RNA-splicing factor PSF/p54 controls DNA-topoisomerase I activity by a direct interactionT Straub
Medizinische Poliklinik, University of Wuerzburg, D 97070 Wuerzburg, Germany
J Biol Chem 273:26261-4. 1998DNA-topoisomerase I has been implied in RNA splicing because it catalyzes RNA strand transfer and activates serine/arginine-rich RNA-splicing factors by phosphorylation... - Human immunodeficiency virus type 1 reverse transcriptase: enhancement of activity by interaction with cellular topoisomerase IH Takahashi
Department of Pathology, National Institute of Health, Tokyo, Japan
Proc Natl Acad Sci U S A 92:5694-8. 1995A number of studies have suggested that topoisomerase I (topo I) activity may be important in human immunodeficiency virus type 1 (HIV-1) replication... - Distinct effects of topoisomerase I and RNA polymerase I inhibitors suggest a dual mechanism of nucleolar/nucleoplasmic partitioning of topoisomerase IMorten O Christensen
Institute of Clinical Chemistry and Laboratory Diagnostics, Heinrich Heine University, Medical School, Moorenstrasse 5, D 40225 Duesseldorf
J Biol Chem 279:21873-82. 2004b>Topoisomerase I is mostly nucleolar, because it plays a preeminent role in ribosomal DNA (rDNA) transcription. It is cleared from nucleoli following exposure to drugs stabilizing covalent DNA intermediates of the enzyme (e.g... - DNA topoisomerase I and PC4 can interact with human TFIIIC to promote both accurate termination and transcription reinitiation by RNA polymerase IIIZ Wang
Laboratory of Biochemistry and Molecular Biology, Rockefeller University, New York, New York 10021, USA
Mol Cell 1:749-57. 1998..Included within the other component are factors, namely DNA topoisomerase I and PC4, previously shown to serve as coactivators for transcription by RNA polymerase II... - Point mutations in the topoisomerase I gene in patients with non-small cell lung cancer treated with irinotecanJunji Tsurutani
Fourth Department of Internal Medicine, Kinki University School of Medicine, Ohonohigashi 377 2, Osakasayama, Osaka 589 8511, Japan
Lung Cancer 35:299-304. 2002..polymerase chain reaction (RT-PCR) single-strand conformation polymorphism analysis was used to detect topoisomerase I (top1) mutations in total RNA from 16 specimens that were excised during surgery from eight patients with non-.. - Analysis of human topoisomerase I inhibition and interaction with the cleavage site +1 deoxyguanosine, via in vitro experiments and molecular modeling studiesGary S Laco
Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA
Bioorg Med Chem 12:5225-35. 2004Human topoisomerase I (Top1) plays a pivotal role in cell replication and transcription, and therefore is an important anti-cancer target... - Tryptophane-205 of human topoisomerase I is essential for camptothecin inhibition of negative but not positive supercoil removalRikke From Frøhlich
Department of Molecular Biology, Aarhus University, C F Møllers Allé Bldg 130, 8000 Arhus C, Denmark
Nucleic Acids Res 35:6170-80. 2007..Since DNA purified from cells is normally under-wound, most studies addressing the relaxation activity of topoisomerase I have utilized negatively supercoiled plasmids... - Sumoylation of topoisomerase I is involved in its partitioning between nucleoli and nucleoplasm and its clearing from nucleoli in response to camptothecinPrasad Rallabhandi
Department of Biochemistry and Molecular Biology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814 4799, USA
J Biol Chem 277:40020-6. 2002Previous studies identified a small fraction of putatively sumoylated topoisomerase I (TOP1) under basal conditions ( approximately 1%), and anticancer camptothecins that trap the TOP1-DNA covalent intermediate markedly increase the .. - Topoisomerase I activity associated with human immunodeficiency virus (HIV) particles and equine infectious anemia virus coreE Priel
Microbiology and Immunology Unit, Faculty of Health Sciences, Ben Gurion University, Beer Sheva, Israel
EMBO J 9:4167-72. 1990In the present study, we found a topoisomerase I (topo I) activity in two strains of human immunodeficiency virus type 1 (HIV-1) and equine infectious anemia virus (EIAV) particles... - BTBD1 and BTBD2 colocalize to cytoplasmic bodies with the RBCC/tripartite motif protein, TRIM5deltaLixin Xu
Department of Biochemistry and Molecular Biology, F Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 4799, USA
Exp Cell Res 288:84-93. 2003We previously identified BTBD1 and BTBD2 as novel topoisomerase I-interacting proteins that share 80% amino acid identity. Here we report the characterization of their subcellular localization... - Interaction between the N-terminal domain of human DNA topoisomerase I and the arginine-serine domain of its substrate determines phosphorylation of SF2/ASF splicing factorE Labourier
Institut de Génétique Moléculaire de Montpellier IGM, UMR 5535 CNRS, Universite Montpellier II, CNRS BP 5051, 1919, route de Mende, F34293 Montpellier Cedex 5, France
Nucleic Acids Res 26:2955-62. 1998Human DNA topoisomerase I, known for its DNA-relaxing activity, is possibly one of the kinases phosphorylating members of the SR protein family of splicing factors, in vivo... - HTLV-1 tax oncoprotein binds to DNA topoisomerase I and inhibits its catalytic activityT Suzuki
Department of Cellular and Molecular Biology, Institute of Medical Science, Tokyo, Japan
Virology 270:291-8. 2000..cellular targets of Tax using a yeast two-hybrid screening system, we isolated a cDNA encoding human DNA topoisomerase I. Tax was demonstrated to bind to topoisomerase I in vitro, and the Tax-topoisomerase I complex was also .. - Par-4 binds to topoisomerase 1 and attenuates its DNA relaxation activityAnindya Goswami
Department of Radiation Medicine, Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40536, USA
Cancer Res 68:6190-8. 2008..Collectively, our findings suggest that Par-4 serves as an intracellular repressor of TOP1 catalytic activity and regulates DNA topology to suppress cellular transformation... - The open state of human topoisomerase I as probed by molecular dynamics simulationGiovanni Chillemi
CASPUR Inter University Consortium for the Application of Super Computing for Universities and Research, Via dei Tizii 6, Rome 00185, Italy
Nucleic Acids Res 35:3032-8. 2007The open state of human topoisomerase I has been probed by molecular dynamics simulation, starting from the coordinates of the closed structure of the protein complexed with DNA, after elimination of the 22-bp DNA duplex oligonucleotide... - The interaction between p53 and DNA topoisomerase I is regulated differently in cells with wild-type and mutant p53C Gobert
Laboratory of Biology and Pharmacology of DNA Topoisomerases, Centre National de la Recherche Scientifique, Unite Mixte de Recherche 8532, Institut Gustave Roussy, PR2, Villejuif 94805 cedex, France
Proc Natl Acad Sci U S A 96:10355-60. 1999DNA topoisomerase I is a nuclear enzyme involved in transcription, recombination, and DNA damage recognition. Previous studies have shown that topoisomerase I interacts directly with the tumor-suppressor protein p53... - Novel insights into catalytic mechanism from a crystal structure of human topoisomerase I in complex with DNAM R Redinbo
Department of Biological Structure and Biomolecular Structure Center, Howard Hughes Medical Institute, University of Washington School of Medicine, Seattle, Washington 98195, USA
Biochemistry 39:6832-40. 2000Human topoisomerase I helps to control the level of DNA supercoiling in cells and is vital for numerous DNA metabolic events, including replication, transcription, and recombination. The 2... - A model for the mechanism of human topoisomerase IL Stewart
Biomolecular Structure Center and Department of Biological Structure, School of Medicine, University of Washington, Seattle, WA 98195 7742, USA
Science 279:1534-41. 1998The three-dimensional structure of a 70-kilodalton amino terminally truncated form of human topoisomerase I in complex with a 22-base pair duplex oligonucleotide, determined to a resolution of 2... - A novel nuclear localization signal in human DNA topoisomerase IY Y Mo
Division of Molecular Pharmacology, Department of Molecular Genetics and Department of Pharmaceutics and Pharmacodynamics, University of Illinois, Chicago, Illinois 60607, USA
J Biol Chem 275:41107-13. 2000..Together, our results suggest that human topo I carries two independent NLSs that have opposite amino acid compositions... - Crystal structures of human topoisomerase I in covalent and noncovalent complexes with DNAM R Redinbo
Biomolecular Structure Center and Department of Biological Structure, Box 357742, School of Medicine, University of Washington, Seattle, WA 98195, USA
Science 279:1504-13. 1998..The crystal structures at 2.1 and 2.5 angstrom resolution of reconstituted human topoisomerase I comprising the core and carboxyl-terminal domains in covalent and noncovalent complexes with 22-base pair DNA .. 
A genetic screen identifies topoisomerase 1 as a regulator of senescenceNicolas Humbert
UMR8161, Institut de Biologie de Lille, Centre National de la Recherche Scientifique Universités de Lille 1 2 Institut Pasteur de Lille, IFR142, Lille, France
Cancer Res 69:4101-6. 2009..We report that knockdown of topoisomerase I (Top1) results in an increased replicative potential associated with a decrease in senescence markers and a ..- Poly(ADP-ribosyl)ation as a DNA damage-induced post-translational modification regulating poly(ADP-ribose) polymerase-1-topoisomerase I interactionTetsu M C Yung
Laboratory of DNA Repair, Health and Environment Unit, Laval University Medical Center, CHUQ, Faculty of Medicine, Laval University, Ste Foy, Quebec G1V 4G2, Canada
J Biol Chem 279:39686-96. 2004..protein-tagged PARP-1 to study this enzyme in live cells and focused on the interaction between PARP-1 and topoisomerase I (Topo I), one of the enzymes that interacts with PARP-1 in vitro... - Detection of topoisomerase I gene point mutation in CPT-11 resistant lung cancer cell lineN Kubota
Pharmacology Division, National Cancer Center Research Institute, Tokyo, Japan
Biochem Biophys Res Commun 188:571-7. 1992CPT-11, a recently developed topoisomerase I (Topo I) inhibitor, attracts the attention not only of basic researchers but also of clinicians because of its high antitumor activity... - Regions within the N-terminal domain of human topoisomerase I exert important functions during strand rotation and DNA bindingRikke From Frøhlich
Department of Molecular Biology, University of Aarhus, CF Møllers Alle, Building 130, DK 8000 Aarhus C, Denmark
J Mol Biol 336:93-103. 2004The human topoisomerase I N-terminal domain is the only part of the enzyme still not crystallized and the function of this domain remains enigmatical... - Topoisomerase I dissociates human immunodeficiency virus type 1 reverse transcriptase from genomic RNAsHidehiro Takahashi
Department of Pathology, National Institute of Infectious Diseases, Toyama 1 23 1, Shinjuku ku, Tokyo 162 8640, Japan
Biochem Biophys Res Commun 313:1073-8. 2004Both HIV-1 reverse transcriptase (RT) and topoisomerase I bind to structural RNAs and they cooperate to synthesize cDNA during the replication of HIV-1... - Residues 190-210 of human topoisomerase I are required for enzyme activity in vivo but not in vitroMorten O Christensen
Institute of Clinical Chemistry and Laboratory Diagnostics, Heinrich Heine University, Medical School, Moorenstrasse 5, D 40225 Duesseldorf, Germany
Nucleic Acids Res 31:7255-63. 2003DNA-topoisomerase I (topo I) unwinds the DNA- double helix by cutting one strand and allowing rotation of the other... - DNA relaxation by human topoisomerase I occurs in the closed clamp conformation of the proteinJames F Carey
Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195, USA
Proc Natl Acad Sci U S A 100:5640-5. 2003In cocrystal structures of human topoisomerase I and DNA, the enzyme is tightly clamped around the DNA helix... - Human DNA topoisomerase I: relaxation, roles, and damage controlJohn B Leppard
Department of Microbiology, School of Medicine, University of Washington, P O Box 357242, 1959 N E Pacific St, Seattle, WA 98195 7242, USA
Chromosoma 114:75-85. 2005Human DNA topoisomerase I is an essential enzyme involved in resolving the torsional stress associated with DNA replication, transcription, and chromatin condensation... - Human topoisomerase I promotes HIV-1 proviral DNA synthesis: implications for the species specificity and cellular tropism of HIV-1 infectionYuko Shoya
Department of Pathology, National Institute of Infectious Diseases, Shinjuku ku, Tokyo 162 8640, Japan
Proc Natl Acad Sci U S A 100:8442-7. 2003..of HIV-1 derived from such cells was only 10-15% of that of human cell-derived virus, expression of human topoisomerase I in the African green monkey cells resulted in a 5-fold increase of the infectivity of progeny HIV-1 virions... - Effect on DNA relaxation of the single Thr718Ala mutation in human topoisomerase I: a functional and molecular dynamics studyGiovanni Chillemi
CASPUR Interuniversities Consortium for Supercomputing Applications Via dei Tizii 6b, Rome 00185, Italy
Nucleic Acids Res 33:3339-50. 2005The functional and dynamical properties of the human topoisomerase I Thr718Ala mutant have been compared to that of the wild-type enzyme using functional assays and molecular dynamics (MD) simulations... - Rotation of DNA around intact strand in human topoisomerase I implies distinct mechanisms for positive and negative supercoil relaxationLevent Sari
Department of Chemistry and The Program in Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA
Nucleic Acids Res 33:6621-34. 2005..An atomic-resolution model for human topoisomerase I in covalent complex with DNA is simulated using molecular dynamics with external potentials that mimic torque .. - Identification of a nucleolin binding site in human topoisomerase IA K Bharti
Division of Cancer Pharmacology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
J Biol Chem 271:1993-7. 1996DNA topoisomerase I (topo I) is involved in the regulation of DNA supercoiling, gene transcription, and rDNA recombination. However, little is known about interactions between topo I and other nuclear proteins... - Mutation at the catalytic site of topoisomerase I in CEM/C2, a human leukemia cell line resistant to camptothecinA Fujimori
Laboratory of Molecular Pharmacology, National Cancer Institute, NIH, Bethesda, Maryland 20892 4255
Cancer Res 55:1339-46. 1995..Resistance is only partially explained by 2-fold reductions in topoisomerase I protein and mRNA levels... - Subnuclear distribution of topoisomerase I is linked to ongoing transcription and p53 statusYinghui Mao
Department of Molecular Genetics, Ohio State University, Columbus, OH 43210, USA
Proc Natl Acad Sci U S A 99:1235-40. 2002The nonconserved, hydrophilic N-terminal domain of eukaryotic DNA topoisomerase I (topo I) is dispensable for catalytic activity in vitro but essential in vivo... - Nucleolar delocalization of human topoisomerase I in response to topotecan correlates with sumoylation of the proteinYin Yuan Mo
Department of Molecular Genetics, University of Illinois, Chicago, Illinois 60607, USA
J Biol Chem 277:2958-64. 2002..Taken together, our results suggest that sumoylation of topo I might serve as an addressing tag for its nucleolar delocalization in response to topo I inhibitors... - Monoclonal antibodies neutralizing mammalian DNA topoisomerase I activityP Oddou
Department of Biology, University of Konstanz, Federal Republic of Germany
Eur J Biochem 177:523-9. 1988..The antibodies are useful for immunocytochemical investigation and for further exploration of the biochemical function of mammalian type-I DNA topoisomerase... - A single mutation in the 729 residue modulates human DNA topoisomerase IB DNA binding and drug resistanceCarmen Losasso
Department of Biology, University of Padova, Via U Bassi 58 B, Padua 35131, Italy
Nucleic Acids Res 36:5635-44. 2008Human DNA topoisomerase I (hTop1p) catalyzes the relaxation of supercoiled DNA and constitutes the cellular target of the antitumor drug camptothecin (CPT)... - Topoisomerase I and ATP activate cDNA synthesis of human immunodeficiency virus type 1Hidehiro Takahashi
Department of Pathology, National Institute of Infectious Diseases, Toyama 1 23 1, Shinjuku ku, Tokyo 162 8640, Japan
Biochem Biophys Res Commun 294:509-17. 2002Replication of human immunodeficiency virus type 1 (HIV-1) is regulated at reverse transcription. Cellular topoisomerase I has been reported to be carried into HIV-1 virions and enhance cDNA synthesis in vitro, suggesting that .. - Interaction between human topoisomerase I and a novel RING finger/arginine-serine proteinP Haluska
Departments of Pharmacology and Medicine, Robert Wood Johnson Medical School, The Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08901, USA
Nucleic Acids Res 27:2538-44. 1999The N-terminus of human topoisomerase I participates in the binding of this enzyme to helicases and other proteins... - Role for nucleolin/Nsr1 in the cellular localization of topoisomerase IT K Edwards
Departments of Medicine Pharmacology, Cancer Institute of New Jersey Robert Wood Johnson Medical School University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey 08901, USA
J Biol Chem 275:36181-8. 2000..In previous work we showed that human nucleolin associates with the N-terminal region of human topoisomerase I (Top1)... - Interaction between the N-terminus of human topoisomerase I and SV40 large T antigenP Haluska
Department of Pharmacology, Robert Wood Johnson Medical School and The Cancer Institute of New Jersey, University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08901, USA
Nucleic Acids Res 26:1841-7. 1998We have attempted to identify human topoisomerase I-binding proteins in order to gain information regarding the cellular roles of this protein and the cytotoxic mechanisms of the anticancer drug camptothecin, which specifically targets .. - Poisoning of human DNA topoisomerase I by ecteinascidin 743, an anticancer drug that selectively alkylates DNA in the minor grooveY Takebayashi
Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4255, USA
Proc Natl Acad Sci U S A 96:7196-201. 1999..human leukemia CEM cells, we purified a 100-kDa protein as a cellular target of Et743 and identified it as topoisomerase I (top1)... - Ecteinascidin 743 induces protein-linked DNA breaks in human colon carcinoma HCT116 cells and is cytotoxic independently of topoisomerase I expressionY Takebayashi
Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892-4255, USA
Clin Cancer Res 7:185-91. 2001..Recently, Et743 DNA adducts have been found to suppress gene expression selectively and to induce topoisomerase I (top1) cleavage complexes in vitro and top1-DNA complexes in cell culture... - Camptothecin sensitivity is mediated by the pleiotropic drug resistance network in yeastR J Reid
Department of Biochemistry and Molecular Pharmacology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
J Biol Chem 272:12091-9. 1997The antineoplastic alkaloid camptothecin interferes with the catalytic cycle of DNA topoisomerase I rendering it a cellular poison... - Two new flavonol glycosides as DNA topoisomerase I poisonsM Lopez-Lazaro
Departamento de Farmacologia, Facultad de Farmacia, Universidad de Sevilla, Espana
Z Naturforsch C 55:898-902. 2000..isolated from a cytotoxic butanol extract from Retama sphaerocarpa Boissier have been assessed to study their topoisomerase I and II activity... - Mdr1/P-glycoprotein, topoisomerase, and glutathione-S-transferase pi gene expression in primary and relapsed state adult and childhood leukaemiasV Gekeler
Physiologisch Chemisches Institut, , Germany
Br J Cancer 66:507-17. 1992..mdr1/P-glycoprotein, DNA topoisomerase II, glutathione-S-transferase pi), and the expression of the DNA topoisomerase I and histone 3.1 genes... - Clinical pharmacokinetics of irinotecanG G Chabot
Pharmacology Laboratory URA 147 CNRS, Gustave Roussy Institute, Villejuif, France
Clin Pharmacokinet 33:245-59. 1997..and its more potent metabolite SN-38 (7- ethyl-10-hydroxy-camptothecin), interfere with mammalian DNA topoisomerase I and cancer cell death appears to result from DNA strand breaks caused by the formation of cleavable complexes... - An in vitro evaluation of human DNA topoisomerase I inhibition by Peganum harmala L. seeds extract and its beta-carboline alkaloidsArmin Madadkar Sobhani
Department of Pharmacology, Iran University of Medical Sciences, Tehran, Iran
J Pharm Pharm Sci 5:19-23. 2002..inhibition by other beta-carbolines like harmane, we have used DNA relaxation assays to investigate topoisomerase I inhibitory activity of P... - Induction of neuronal apoptosis by camptothecin, an inhibitor of DNA topoisomerase-I: evidence for cell cycle-independent toxicityE J Morris
Department of Pharmacology, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, Piscataway 08854, USA
J Cell Biol 134:757-70. 1996..We suggest a model based on transcriptionally mediated DNA damage, a novel mechanism of action of topo-I poisons... - Increased susceptibility of spinal muscular atrophy fibroblasts to camptothecin is p53-independentChia Yen Wu
Nemours Biomedical Research, Alfred I, duPont Hospital for Children, Wilmington, DE, USA
BMC Cell Biol 10:40. 2009..Previously, we have shown that skin fibroblasts from SMA patients are more sensitive to the DNA topoisomerase I inhibitor camptothecin, supporting a role for SMN in cell survival... - Synthesis of new indeno[1,2-c]isoquinolines: cytotoxic non-camptothecin topoisomerase I inhibitorsM Cushman
Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907, USA
J Med Chem 43:3688-98. 2000In an attempt to design and synthesize potential anticancer agents acting by inhibition of topoisomerase I (top1), a new series of indenoisoquinolines was prepared and tested for cytotoxicity in human cancer cell cultures and for .. - Cloning of Chinese hamster DNA topoisomerase I cDNA and identification of a single point mutation responsible for camptothecin resistanceA Tanizawa
Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892
J Biol Chem 268:25463-8. 1993..Chinese hamster cell line that contains a catalytically altered and camptothecin (CPT)-resistant DNA topoisomerase I (top 1) (Tanizawa, A., and Pommier, Y. (1992) Cancer Res... - Novel missense mutation of the DNA topoisomerase I gene in SN-38-resistant DLD-1 cellsYasuhiro Arakawa
Department of Molecular Genetics, Institute of DNA Medicine, Jikei University School of Medicine, Nishi Shimbashi 3 25 8 Minato ku, Tokyo 105 8461, Japan
Mol Cancer Ther 5:502-8. 2006..DLDSNR6 cells carried a missense mutation in one allele of the DNA topoisomerase I gene that substituted glycine for serine at amino acid residue 365 accompanied by loss of the latter part of .. - SCT1 mutants suppress the camptothecin sensitivity of yeast cells expressing wild-type DNA topoisomerase IE A Kauh
Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA
Proc Natl Acad Sci U S A 92:6299-303. 1995Camptothecin is a potent antineoplastic agent that interferes with the action of eukaryotic DNA topoisomerase I; the covalent enzyme-DNA intermediate is reversibly stabilized, leading to G2 arrest and cell death... - Nucleolar function and size in cancer cellsM Derenzini
Department of Experimental Pathology, S Orsola Hospital, University of Bologna, Italy
Am J Pathol 152:1291-7. 1998..by measuring RNA polymerase I activity and expression of RNA polymerase I upstream binding factor (UBF), DNA topoisomerase I, and fibrillarin, three proteins involved in synthesis and processing of rRNA... - Silatecan DB-67 is a novel DNA topoisomerase I-targeted radiation sensitizerAllan Y Chen
Department of Radiation Oncology, University of California Davis Medical Center, Sacramento, CA 95817, USA
Mol Cancer Ther 4:317-24. 2005..DB-67) represents a new generation of camptothecin derivatives that exhibits a potent in vitro DNA topoisomerase I (TOP1)-mediated DNA-damaging activity, improved blood stability, and holds significant promise for the .. - Action models for the antitumor drug camptothecin: formation of alkali-labile complex with DNA and inhibition of human DNA topoisomerase ISergei A Streltsov
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 32 Vavilov St, Moscow 119991, Russia
J Biomol Struct Dyn 20:447-54. 2002..its derivatives, including water-soluble topotecan (TPT), is determined by their ability to inhibit human DNA topoisomerase I (top 1). On the other hand, TPT has been recently shown to bind to DNA... - Mutation of Gly721 alters DNA topoisomerase I active site architecture and sensitivity to camptothecinMarie van der Merwe
Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
J Biol Chem 283:3305-15. 2008DNA topoisomerase I (Top1p) catalyzes the relaxation of supercoiled DNA via a concerted mechanism of DNA strand cleavage and religation... - The effects of camptothecin on RNA polymerase II transcription: roles of DNA topoisomerase IGiovanni Capranico
Department of Biochemistry, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy
Biochimie 89:482-9. 2007Eukaryotic DNA topoisomerase I is active in transcribed chromatin domains to modulate transcription-generated DNA torsional tension... - Dissecting the transcriptional functions of human DNA topoisomerase I by selective inhibitors: implications for physiological and therapeutic modulation of enzyme activityGiovanni Capranico
G Moruzzi Department of Biochemistry, University of Bologna, Bologna, Italy
Biochim Biophys Acta 1806:240-50. 2010Camptothecin is a selective inhibitor of DNA topoisomerase I, and has effective antitumor activity... - Characterisation of two intronic nuclear-matrix-attachment regions in the human DNA topoisomerase I geneH Romig
Department of Biology, University of Konstanz, Germany
Eur J Biochem 221:411-9. 1994We identify two high-affinity matrix-attachment regions (MAR elements) located in two introns of the human DNA topoisomerase I gene (TOP1)... - Low-level resistance to camptothecin in a human small-cell lung cancer cell line without reduction in DNA topoisomerase I or drug-induced cleavable complex formationM Sorensen
Laboratory of Experimental Medical Oncology, The Finsen Center, Rigshospitalet, Copenhagen, Denmark
Br J Cancer 77:2152-61. 1998..NYH/CAM50 cells had reduced topoisomerase I (topo I) content and activity, and consequently CPT-induced DNA single strand breaks (SSBs) were reduced, as .. - Differential poisoning of human and Aspergillus nidulans DNA topoisomerase I by bi- and terbenzimidazolesG H Goldman
Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Brazil
Biochemistry 36:6488-94. 1997DNA topoisomerase I has been partially purified from Aspergillus nidulans. The purified enzyme is most likely the major nuclear DNA topoisomerase I on the basis of the following findings... - The level of anti-topoisomerase I antibodies highly correlates with metacarpophalangeal and proximal interphalangeal joints flexion contractures in patients with systemic sclerosisM Radic
Department of Internal Medicine, Clinical Hospital Split, Split, Croatia
Clin Exp Rheumatol 24:407-12. 2006It is found that an antibody directed against DNA topoisomerase I (anti-topo I abs) is detected almost exclusively in systemic sclerosis (SSc). These antibodies are predictors of pulmonary fibrosis and peripheral vascular disease. - Genome-wide analysis of novel splice variants induced by topoisomerase I poisoning shows preferential occurrence in genes encoding splicing factorsStéphanie Solier
Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892 4255, USA
Cancer Res 70:8055-65. 2010..RNA splicing is required to remove introns from pre-mRNA, and alternative splicing generates protein diversity. Topoisomerase I (Top1) has been shown to be coupled with splicing by regulating serine/arginine-rich splicing proteins... - Nonclassic functions of human topoisomerase I: genome-wide and pharmacologic analysesZe Hong Miao
Laboratories of Molecular Pharmacology, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA
Cancer Res 67:8752-61. 2007The biological functions of nuclear topoisomerase I (Top1) have been difficult to study because knocking out TOP1 is lethal in metazoans... - Clinical pharmacokinetics of topotecanV M Herben
Department of Pharmacy and Pharmacology, Netherlands Cancer Institute, Amsterdam, The Netherlands
Clin Pharmacokinet 31:85-102. 1996Topotecan (Hycamtin), a semisynthetic water-soluble derivative of camptothecin, is a potent inhibitor of DNA topoisomerase I in vitro and has demonstrated encouraging antitumour activity in a wide variety of tumours, including ovarian .. - Position-specific trapping of topoisomerase I-DNA cleavage complexes by intercalated benzo[a]- pyrene diol epoxide adducts at the 6-amino group of adenineY Pommier
Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Proc Natl Acad Sci U S A 97:10739-44. 2000DNA topoisomerase I (top1) is the target of potent anticancer agents, including camptothecins and DNA intercalators, which reversibly stabilize (trap) top1 catalytic intermediates (cleavage complexes)... - Effect of some bis Mannich bases and corresponding piperidinols on DNA topoisomerase IPakize Canturk
Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Ege University, Izmir, Turkey
Arzneimittelforschung 58:686-91. 2008..C1, C2 and C5), which are the structural isomers of B1, B2 and B5, were synthesized and their effects on DNA topoisomerase I were tested... - An insight into the mechanism of inhibition of unusual bi-subunit topoisomerase I from Leishmania donovani by 3,3'-di-indolylmethane, a novel DNA topoisomerase I poison with a strong binding affinity to the enzymeAmit Roy
Department of Molecular Parasitology, Indian Institute of Chemical Biology, 4 Raja S C Mullick Road, Kolkata 700032, India
Biochem J 409:611-22. 2008..In the present study, we show that DIM is a potent inhibitor of Leishmania donovani topoisomerase I with an IC50 of 1.2 microM... - Pea DNA topoisomerase I is phosphorylated and stimulated by casein kinase 2 and protein kinase CNarendra Tuteja
International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, P O Box 10504, New Delhi 110 067, India
Plant Physiol 132:2108-15. 2003DNA topoisomerase I catalyzes the relaxation of superhelical DNA tension and is vital for DNA metabolism; therefore, it is essential for growth and development of plants... - Analysis of DNA relaxation and cleavage activities of recombinant Mycobacterium tuberculosis DNA topoisomerase I from a new expression and purification protocolThirunavukkarasu Annamalai
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York, USA
BMC Biochem 10:18. 2009Mycobacterium tuberculosis DNA topoisomerase I is an attractive target for discovery of novel TB drugs that act by enhancing the accumulation of the topoisomerase-DNA cleavage product... - Thermotoga maritima-Escherichia coli chimeric topoisomerases. Answers about involvement of the carboxyl-terminal domain in DNA topoisomerase I-mediated catalysisThierry Viard
Laboratoire d Enzymologie des Acides Nucleiques, Institut de Genetique et Microbiologie, UMR 8621 CNRS, Batiment 400, Universite Paris Sud, Centre d Orsay, 91405 Orsay, France
J Biol Chem 279:30073-80. 2004..For this purpose, we prepared various recombinant topoisomerases from two model enzymes: topoisomerase I from the hyperthermophilic bacterium Thermotoga maritima and topoisomerase I from Escherichia coli... - The deubiquitinating enzyme Doa4p protects cells from DNA topoisomerase I poisonsPaola Fiorani
Department of Molecular Pharmacology, St Jude Children s Research Hospital, 332 N Lauderdale, Memphis, TN 38105, USA
J Biol Chem 279:21271-81. 2004DNA topoisomerase I (Top1p) catalyzes changes in DNA topology via the formation of an enzyme-DNA covalent complex that is reversibly stabilized by the antitumor drug, camptothecin (CPT)... - Poly(ADPR)polymerase-1 signalling of the DNA damage induced by DNA topoisomerase I poison in D54(p53wt) and U251(p53mut) glioblastoma cell linesGabriella Cimmino
Department of Functional and Structural Biology, University Federico II, Naples, Italy
Pharmacol Res 55:49-56. 2007..widely characterised by the mutation of the p53 gene and p53 disruption sensitizes glioblastoma cells to DNA topoisomerase I (TOPO I) inhibitor-mediated apoptosis... - Therapeutic activity of CPT-11, a DNA-topoisomerase I inhibitor, against peripheral primitive neuroectodermal tumour and neuroblastoma xenograftsG Vassal
Department of Pediatric Oncology, Institut Gustave Roussy, Villejuif, France
Br J Cancer 74:537-45. 1996The anti-tumour activity of CPT-11, a topoisomerase I inhibitor, was evaluated in four human neural-crest-derived paediatric tumour xenografts; one peripheral primitive neuroectodermal tumour (pPNET) (SK-N-MC) and three neuroblastomas... - Repair of topoisomerase I covalent complexes in the absence of the tyrosyl-DNA phosphodiesterase Tdp1Chunyan Liu
Laboratory of Molecular Biology, National Institute of Mental Health, Bethesda, MD 20892 4034, USA
Proc Natl Acad Sci U S A 99:14970-5. 2002Accidental or drug-induced interruption of the breakage and reunion cycle of eukaryotic topoisomerase I (Top1) yields complexes in which the active site tyrosine of the enzyme is covalently linked to the 3' end of broken DNA... - Targeting to transcriptionally active loci by the hydrophilic N-terminal domain of Drosophila DNA topoisomerase IW L Shaiu
Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
Mol Cell Biol 18:4358-67. 1998DNA topoisomerase I (topo I) from Drosophila melanogaster contains a nonconserved, hydrophilic N-terminal domain of about 430 residues upstream of the conserved core domains... - Topoisomerase I-mediated DNA cleavage induced by the minor groove-directed binding of bibenzimidazoles to a distal siteQasim A Khan
Department of Pharmacology, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854 5635, USA
J Mol Biol 365:561-9. 2007Many agents (e.g. camptothecins, indolocarbazoles, indenoisoquinolines, and dibenzonaphthyridines) stimulate topoisomerase I (TOP1)-mediated DNA cleavage (a behavior termed topoisomerase I poisoning) by interacting with both the DNA and .. - Characterisation of a human small-cell lung cancer cell line resistant to the DNA topoisomerase I-directed drug topotecanM Sorensen
Department of Pathology, Sundby Hospital, Copenhagen, Denmark
Br J Cancer 72:399-404. 1995Camptothecins are DNA topoisomerase I-directed anti-tumour drugs with a novel mechanism of action... - Chemotherapy with irinotecan (CPT-11), a topoisomerase-I inhibitor, for refractory and relapsed non-Hodgkin's lymphomaT Takagi
Division of Laboratory Medicine, Chiba Cancer Center Hospital, Japan
Leuk Lymphoma 42:577-86. 2001..A superior salvage chemotherapy regimen could be found in the future by investigating combinations of low-dose CPT-11 and cisplatin or topoisomerase-II inhibitors... - A quantitative RT-PCR method to determine topoisomerase I mRNA levels in human tissue samplesKarine Durand-Faucher
Department of Biochemistry and Molecular Genetics, CHU Dupuytren, Limoges, France
Clin Chem Lab Med 43:707-14. 2005DNA topoisomerase I (Topo I) is involved in DNA replication, transcription, recombination and repair... - Induction of radiosensitization by indolocarbazole derivatives: the role of DNA topoisomerase IAllan Y Chen
Department of Radiation Oncology, UC Davis Medical Center, 4501 X Street, G 126, Sacramento, CA 95817, USA
Mol Pharmacol 66:553-60. 2004DNA topoisomerase I (TOP1) mediates the induction of radiosensitization (RS) by camptothecin derivatives in mammalian cells. Many indolocarbazole (INDO) derivatives have been shown to induce TOP1-mediated DNA damage (T1DD)... - DNA topoisomerase I in oncology: Dr Jekyll or Mr Hyde?A K Larsen
Institut Gustave Roussy, Laboratory of Biology and Pharmacology of DNA Topoisomerases 39, rue Camille Desmoulins, Villejuif, 94805, France
Pathol Oncol Res 5:171-8. 1999Mammalian DNA topoisomerase I is a multifunctional enzyme which is essential for embryonal development... - Isolation and characterization of a gene encoding DNA topoisomerase I in Drosophila melanogasterT S Hsieh
Department of Biochemistry, Duke University Medical Center, Durham, NC 27710
Nucleic Acids Res 20:6177-82. 1992We synthesized a DNA probe specific for the gene encoding eucaryotic DNA topoisomerase I by the polymerase chain reaction... - CDC45 and DPB11 are required for processive DNA replication and resistance to DNA topoisomerase I-mediated DNA damageR J Reid
Department of Biochemistry, Thomas Jefferson University, Philadelphia, PA 19107, USA
Proc Natl Acad Sci U S A 96:11440-5. 1999The antitumor agent camptothecin targets DNA topoisomerase I by reversibly stabilizing a covalent enzyme-DNA intermediate... - Reduced expression of DNA topoisomerase I in SF295 human glioblastoma cells selected for resistance to homocamptothecin and diflomotecanZhiYong Liao
Laboratory of Molecular Pharmacology, Bldg, 37, Rm 5068, National Institutes of Health, Bethesda, MD 20892 4255, USA
Mol Pharmacol 73:490-7. 2008Homocamptothecins (hCPTs) are a novel class of topoisomerase I (Top1) inhibitors with enhanced chemical stability compared with the currently used camptothecin (CPT) analogs irinotecan and topotecan... - DNA topoisomerase i as a transcription protein and a lethal cellular toxinLuca Lotito
Department of Biochemistry, University of Bologna, Bologna, Italy
Ital J Biochem 56:122-9. 2007DNA topoisomerase I constitutes a significant relaxing activity in nuclei of eukaryotic cells. The enzyme acts during several DNA transactions involving the generation of torsional stress in the DNA template... - Camptothecins and topoisomerase I: a foot in the door. Targeting the genome beyond topoisomerase I with camptothecins and novel anticancer drugs: importance of DNA replication, repair and cell cycle checkpointsYves Pommier
Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA
Curr Med Chem Anticancer Agents 4:429-34. 2004Camptothecins selectively target topoisomerase I (Top1) by trapping the catalytic intermediate of the Top1-DNA reaction, the cleavage complex. Hence, camptothecins represent a paradigm for targeting macromolecular interactions... - IgM, IgG, and IgA anti-DNA topoisomerase I antibodies in systemic sclerosisErasmo Martínez-Cordero
Laboratory of Research in Autoimmunity, Mexico
J Clin Lab Anal 23:408-16. 2009Anti-DNA topoisomerase I (anti-topo I) antibodies have been broadly studied in systemic sclerosis (SSc)... - Azaindenoisoquinolines as topoisomerase I inhibitors and potential anticancer agents: a systematic study of structure-activity relationshipsEvgeny Kiselev
Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, and the Purdue Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907, United States
J Med Chem 55:1682-97. 2012A comprehensive study of a series of azaindenoisoquinoline topoisomerase I (Top1) inhibitors is reported. The synthetic pathways have been developed to prepare 7-, 8-, 9-, and 10-azaindenoisoquinolines... - The antitumor and antimetastatic effects of N-trimethyl chitosan-encapsulated camptothecin on ovarian cancer with minimal side effectsLina Zhou
Department of Gynecology and Obstetrics, West China Second Hospital, Sichuan University, Chengdu, P R China
Oncol Rep 24:941-8. 2010..promising activity for the treatment of solid tumors because of its specific inhibition of eukaryotic DNA topoisomerase I. Yet, its application is hindered due to extreme water insolubility and severe side effects... - Human topoisomerase I forms double cleavage complexes on natural DNAKent Søe
Leibniz Institute for Age Research, Fritz Lipmann Institute FLI, Biochemical Group, Beutenbergstrasse 11, D 07745 Jena, Germany
Biochem Biophys Res Commun 349:178-85. 2006DNA topoisomerase I releases torsional stress generated in chromatin during transcription and replication...
Research Grants
- TOPOISOMERASE I AS AN ANTITUMOR DRUG TARGETPETER D ARPA; Fiscal Year: 2003..The proposed research focuses on the molecular responses to camptothecin-DNA-topoisomerase I complexes...
- DNA TOPOISOMERASE-CAMPTOTHECIN INTERACTIONSMary Ann Bjornsti; Fiscal Year: 2007DNA topoisomerase I (Top1) plays important roles in DNA replication, transcription and recombination, by catalyzing changes in DNA topology through a mechanism of transient DNA strand breakage and rejoining...
- SAR OF NOVEL TOPO I INHIBITOR AGAINST PROSTATE CANCERYUE WEI LEE; Fiscal Year: 2001..Alpha-Boswellic acid acetate shows excellent inhibitory activity against the DNA topoisomerase I enzyme: It is 3 times more potent than the standard, camptothecin, in the topoisomerase I relaxation assay...
- Benzo[i]phenanthridines: TOP1-Targeting Antitumor AgentsEDMOND LAVOIE; Fiscal Year: 2006b>Topoisomerase I (TOP1) is an enzyme that alters the topology of DNA by transiently breaking one DNA strand...
- Novel Mechanisms by which RAD18 and POLZ affect Response to Anticancer AgentsCHRISTINE ELIZABETH CANMAN; Fiscal Year: 2010Drugs which target DNA through direct crosslinking or trapping of topoisomerase I (TOP1) complexes are some of the most effective treatments for cancer...
- VACCINIA VIRUS DNA TOPOISOMERASE IStewart Shuman; Fiscal Year: 1993..The third approach, genetically based, will be to isolate virus mutants affected conditionally in DNA topoisomerase activity so as to understand more fully the physiologic role of this enzyme in vivo...
- DNA TOPOISOMERASE-CAMPTOTHECIN INTERACTIONSMary Ann Bjornsti; Fiscal Year: 2010DNA topoisomerase I (Top1) plays important roles in DNA replication, transcription and recombination, by catalyzing changes in DNA topology through a mechanism of transient DNA strand breakage and rejoining...
- MECHANISMS OF SUPPRESSING CAMPTOTHECIN TOXICITYMary Ann Bjornsti; Fiscal Year: 2003DESCRIPTION: (Applicant's Abstract) In recent years, DNA topoisomerase I (Top1) has emerged as the cellular target of an increasing number of antitumor agents...
- SUMOylation and Cell Sensitivity to Top1 PoisonsMary Ann Bjornsti; Fiscal Year: 2009Eukaryotic DNA topoisomerase I (Top1p) plays important roles in DNA replication, transcription and recombination, and catalyzes changes in DNA topology through the transient breakage and rejoining of a single DNA strand in duplex DNA...
- DNA Topoisomerase Camptothecin InteractionsMary Ann Bjornsti; Fiscal Year: 2005DESCRIPTION (PROVIDED BY APPLICANT): DNA topoisomerase I (Top1p) plays an important role in DNA replication, transcription and recombination...
- DNA TOPOISOMERASE I TARGET INTERACTIONS OF CAMPTOTHECINSDanzhou Yang; Fiscal Year: 2004..anticancer agent renowned for its novel mechanism of action, the inhibition of DNA- processing enzyme topoisomerase I. Two camptothecins (TPT and CPT-11) have recently gained the U.S...
- MECHANISM OF ACTION OF ANTITUMOR DRUGSLeroy F Liu; Fiscal Year: 2010The long-term goal of this application is to understand the mechanism of action of topoisomerase I (Top1)-targeting drugs. Camptothecins (CPTs) (e.g...