topoisomerase I

Summary

Gene Symbol: topoisomerase I
Description: topoisomerase (DNA) I
Alias: TOPI, DNA topoisomerase 1, type I DNA topoisomerase
Species: human

Top Publications

  1. ncbi [Topotecan: a new field of use]
    S Ferrari
    , Pavia
    Tumori 85:S23-8. 1999
  2. ncbi 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 domain
    A Ueki
    Department of Hygiene, Kawasaki Medical School, Kurashiki, Japan
    Immunobiology 204:458-65. 2001
  3. pmc Topoisomerase 1 and single-strand break repair modulate transcription-induced CAG repeat contraction in human cells
    Leroy 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
  4. doi Selective oxidation of DNA topoisomerase 1 induces systemic sclerosis in the mouse
    Amélie Servettaz
    Universite Paris Descartes, Faculte de Medecine, EA1833, Paris, France
    J Immunol 182:5855-64. 2009
  5. pmc The mechanism of topoisomerase I poisoning by a camptothecin analog
    Bart 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. 2002
  6. pmc SUMO-1 conjugation to topoisomerase I: A possible repair response to topoisomerase-mediated DNA damage
    Y 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. 2000
  7. doi Poly(ADP-ribose) polymerase signaling of topoisomerase 1-dependent DNA damage in carcinoma cells
    Giovanna D'Onofrio
    Department of Structural and Functional Biology, University Federico II of Naples, Italy
    Biochem Pharmacol 81:194-202. 2011
  8. pmc Tyrosyl-DNA phosphodiesterase 1 (TDP1) repairs DNA damage induced by topoisomerases I and II and base alkylation in vertebrate cells
    Junko Murai
    Department of Radiation Genetics, Kyoto University Graduate School of Medicine, Yoshida Konoe, Sakyo ku, Kyoto 606 8501, Japan
    J Biol Chem 287:12848-57. 2012
  9. ncbi SUMO-1 conjugation to intact DNA topoisomerase I amplifies cleavable complex formation induced by camptothecin
    Koji Horie
    Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo ku, Japan
    Oncogene 21:7913-22. 2002
  10. ncbi Role for nucleolin/Nsr1 in the cellular localization of topoisomerase I
    T 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

Research Grants

  1. TOPOISOMERASE I AS AN ANTITUMOR DRUG TARGET
    PETER D ARPA; Fiscal Year: 2003
  2. DNA TOPOISOMERASE-CAMPTOTHECIN INTERACTIONS
    Mary Ann Bjornsti; Fiscal Year: 2007
  3. SAR OF NOVEL TOPO I INHIBITOR AGAINST PROSTATE CANCER
    YUE WEI LEE; Fiscal Year: 2001
  4. Benzo[i]phenanthridines: TOP1-Targeting Antitumor Agents
    EDMOND LAVOIE; Fiscal Year: 2006
  5. Novel Mechanisms by which RAD18 and POLZ affect Response to Anticancer Agents
    CHRISTINE ELIZABETH CANMAN; Fiscal Year: 2010
  6. VACCINIA VIRUS DNA TOPOISOMERASE I
    Stewart Shuman; Fiscal Year: 1993
  7. DNA TOPOISOMERASE-CAMPTOTHECIN INTERACTIONS
    Mary Ann Bjornsti; Fiscal Year: 2010
  8. MECHANISMS OF SUPPRESSING CAMPTOTHECIN TOXICITY
    Mary Ann Bjornsti; Fiscal Year: 2003
  9. DNA Topoisomerase Camptothecin Interactions
    Mary Ann Bjornsti; Fiscal Year: 2005
  10. SUMOylation and Cell Sensitivity to Top1 Poisons
    Mary Ann Bjornsti; Fiscal Year: 2009

Detail Information

Publications192 found, 100 shown here

  1. ncbi [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...
  2. ncbi 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 domain
    A Ueki
    Department of Hygiene, Kawasaki Medical School, Kurashiki, Japan
    Immunobiology 204:458-65. 2001
    Autoantibodies 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 ..
  3. pmc Topoisomerase 1 and single-strand break repair modulate transcription-induced CAG repeat contraction in human cells
    Leroy 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...
  4. doi Selective oxidation of DNA topoisomerase 1 induces systemic sclerosis in the mouse
    Amélie Servettaz
    Universite Paris Descartes, Faculte de Medecine, EA1833, Paris, France
    J Immunol 182:5855-64. 2009
    ..limited SSc, whereas hypochlorite or hydroxyl radicals induced cutaneous and lung fibrosis and anti-DNA topoisomerase 1 autoantibodies that characterize human diffuse SSc...
  5. pmc The mechanism of topoisomerase I poisoning by a camptothecin analog
    Bart 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. 2002
    We 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...
  6. pmc SUMO-1 conjugation to topoisomerase I: A possible repair response to topoisomerase-mediated DNA damage
    Y 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. 2000
    Ubiquitin/26S proteasome-dependent degradation of topoisomerase I (TOP1) has been suggested to be a unique repair response to TOP1-mediated DNA damage...
  7. doi Poly(ADP-ribose) polymerase signaling of topoisomerase 1-dependent DNA damage in carcinoma cells
    Giovanna D'Onofrio
    Department of Structural and Functional Biology, University Federico II of Naples, Italy
    Biochem Pharmacol 81:194-202. 2011
    ..The characterization of such signaling network can be relevant to a strategy aimed at overcoming acquired chemoresistance to TOP1 inhibitors...
  8. pmc Tyrosyl-DNA phosphodiesterase 1 (TDP1) repairs DNA damage induced by topoisomerases I and II and base alkylation in vertebrate cells
    Junko Murai
    Department of Radiation Genetics, Kyoto University Graduate School of Medicine, Yoshida Konoe, Sakyo ku, Kyoto 606 8501, Japan
    J Biol Chem 287:12848-57. 2012
    Tyrosyl-DNA phosphodiesterase 1 (Tdp1) repairs topoisomerase I cleavage complexes (Top1cc) by hydrolyzing their 3'-phosphotyrosyl DNA bonds and repairs bleomycin-induced DNA damage by hydrolyzing 3'-phosphoglycolates...
  9. ncbi SUMO-1 conjugation to intact DNA topoisomerase I amplifies cleavable complex formation induced by camptothecin
    Koji Horie
    Institute of Molecular and Cellular Biosciences, University of Tokyo, Bunkyo ku, Japan
    Oncogene 21:7913-22. 2002
    DNA 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)...
  10. ncbi Role for nucleolin/Nsr1 in the cellular localization of topoisomerase I
    T 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)...
  11. ncbi NKX3.1 homeodomain protein binds to topoisomerase I and enhances its activity
    Cai Bowen
    Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, District of Columbia 20007 2197, USA
    Cancer Res 67:455-64. 2007
    ..Using an NKX3.1 affinity column, we isolated topoisomerase I (Topo I) from a PC-3 prostate cancer cell extract...
  12. pmc Reverse Transcriptase and Cellular Factors: Regulators of HIV-1 Reverse Transcription
    Kylie Warren
    Division of Infectious Diseases, Queensland Institute of Medical Research, Brisbane, QLD, Australia E Mails K W D W L M
    Viruses 1:873-94. 2009
    ..In addition, recent studies implicate the cellular proteins HuR, AKAP149, and DNA topoisomerase I in reverse transcription through an interaction with RT...
  13. doi Overexpression of Lewis(y) antigen protects ovarian cancer RMG-1 cells from carboplatin-induced apoptosis by the upregulation of Topo-I and Topo-II β
    Changzhi Wang
    Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, People s Republic of China
    Anat Rec (Hoboken) 294:961-9. 2011
    ..Therefore, the inhibition of Lewis (y) antigen may be a novel strategy of cancer chemotherapy...
  14. ncbi Distinct effects of topoisomerase I and RNA polymerase I inhibitors suggest a dual mechanism of nucleolar/nucleoplasmic partitioning of topoisomerase I
    Morten 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. 2004
    b>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...
  15. pmc Tryptophane-205 of human topoisomerase I is essential for camptothecin inhibition of negative but not positive supercoil removal
    Rikke 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...
  16. ncbi Point mutations in the topoisomerase I gene in patients with non-small cell lung cancer treated with irinotecan
    Junji 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-..
  17. pmc The histone variant mH2A1.1 interferes with transcription by down-regulating PARP-1 enzymatic activity
    Khalid 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...
  18. ncbi DNA topoisomerase I and PC4 can interact with human TFIIIC to promote both accurate termination and transcription reinitiation by RNA polymerase III
    Z 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...
  19. ncbi Nucleolar delocalization of human topoisomerase I in response to topotecan correlates with sumoylation of the protein
    Yin 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...
  20. pmc A single mutation in the 729 residue modulates human DNA topoisomerase IB DNA binding and drug resistance
    Carmen Losasso
    Department of Biology, University of Padova, Via U Bassi 58 B, Padua 35131, Italy
    Nucleic Acids Res 36:5635-44. 2008
    Human DNA topoisomerase I (hTop1p) catalyzes the relaxation of supercoiled DNA and constitutes the cellular target of the antitumor drug camptothecin (CPT)...
  21. ncbi Single mutation in the linker domain confers protein flexibility and camptothecin resistance to human topoisomerase I
    Paola Fiorani
    Department of Biology, University of Padua, Via U Bassi 58 B, Padua 35131, Italy
    J Biol Chem 278:43268-75. 2003
    DNA 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...
  22. pmc Human immunodeficiency virus type 1 reverse transcriptase: enhancement of activity by interaction with cellular topoisomerase I
    H Takahashi
    Department of Pathology, National Institute of Health, Tokyo, Japan
    Proc Natl Acad Sci U S A 92:5694-8. 1995
    A number of studies have suggested that topoisomerase I (topo I) activity may be important in human immunodeficiency virus type 1 (HIV-1) replication...
  23. pmc Subnuclear distribution of topoisomerase I is linked to ongoing transcription and p53 status
    Yinghui Mao
    Department of Molecular Genetics, Ohio State University, Columbus, OH 43210, USA
    Proc Natl Acad Sci U S A 99:1235-40. 2002
    The nonconserved, hydrophilic N-terminal domain of eukaryotic DNA topoisomerase I (topo I) is dispensable for catalytic activity in vitro but essential in vivo...
  24. ncbi The RNA-splicing factor PSF/p54 controls DNA-topoisomerase I activity by a direct interaction
    T Straub
    Medizinische Poliklinik, University of Wuerzburg, D 97070 Wuerzburg, Germany
    J Biol Chem 273:26261-4. 1998
    DNA-topoisomerase I has been implied in RNA splicing because it catalyzes RNA strand transfer and activates serine/arginine-rich RNA-splicing factors by phosphorylation...
  25. ncbi Analysis of human topoisomerase I inhibition and interaction with the cleavage site +1 deoxyguanosine, via in vitro experiments and molecular modeling studies
    Gary 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. 2004
    Human topoisomerase I (Top1) plays a pivotal role in cell replication and transcription, and therefore is an important anti-cancer target...
  26. ncbi Sumoylation of topoisomerase I is involved in its partitioning between nucleoli and nucleoplasm and its clearing from nucleoli in response to camptothecin
    Prasad 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. 2002
    Previous 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 ..
  27. pmc Topoisomerase I activity associated with human immunodeficiency virus (HIV) particles and equine infectious anemia virus core
    E Priel
    Microbiology and Immunology Unit, Faculty of Health Sciences, Ben Gurion University, Beer Sheva, Israel
    EMBO J 9:4167-72. 1990
    In 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...
  28. ncbi BTBD1 and BTBD2 colocalize to cytoplasmic bodies with the RBCC/tripartite motif protein, TRIM5delta
    Lixin 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. 2003
    We 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...
  29. ncbi Novel insights into catalytic mechanism from a crystal structure of human topoisomerase I in complex with DNA
    M 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. 2000
    Human 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...
  30. ncbi Identification of a nucleolin binding site in human topoisomerase I
    A K Bharti
    Division of Cancer Pharmacology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 271:1993-7. 1996
    DNA 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...
  31. pmc Human topoisomerase I promotes HIV-1 proviral DNA synthesis: implications for the species specificity and cellular tropism of HIV-1 infection
    Yuko 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...
  32. ncbi Topoisomerase I dissociates human immunodeficiency virus type 1 reverse transcriptase from genomic RNAs
    Hidehiro 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. 2004
    Both HIV-1 reverse transcriptase (RT) and topoisomerase I bind to structural RNAs and they cooperate to synthesize cDNA during the replication of HIV-1...
  33. ncbi Regions within the N-terminal domain of human topoisomerase I exert important functions during strand rotation and DNA binding
    Rikke 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. 2004
    The human topoisomerase I N-terminal domain is the only part of the enzyme still not crystallized and the function of this domain remains enigmatical...
  34. ncbi A novel nuclear localization signal in human DNA topoisomerase I
    Y 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...
  35. ncbi HTLV-1 tax oncoprotein binds to DNA topoisomerase I and inhibits its catalytic activity
    T 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 ..
  36. pmc Residues 190-210 of human topoisomerase I are required for enzyme activity in vivo but not in vitro
    Morten 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. 2003
    DNA-topoisomerase I (topo I) unwinds the DNA- double helix by cutting one strand and allowing rotation of the other...
  37. ncbi Crystal structures of human topoisomerase I in covalent and noncovalent complexes with DNA
    M 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 ..
  38. ncbi Detection of topoisomerase I gene point mutation in CPT-11 resistant lung cancer cell line
    N Kubota
    Pharmacology Division, National Cancer Center Research Institute, Tokyo, Japan
    Biochem Biophys Res Commun 188:571-7. 1992
    CPT-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...
  39. doi A genetic screen identifies topoisomerase 1 as a regulator of senescence
    Nicolas 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 ..
  40. ncbi A model for the mechanism of human topoisomerase I
    L Stewart
    Biomolecular Structure Center and Department of Biological Structure, School of Medicine, University of Washington, Seattle, WA 98195 7742, USA
    Science 279:1534-41. 1998
    The 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...
  41. pmc Par-4 binds to topoisomerase 1 and attenuates its DNA relaxation activity
    Anindya 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...
  42. pmc The open state of human topoisomerase I as probed by molecular dynamics simulation
    Giovanni 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. 2007
    The 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...
  43. pmc Effect on DNA relaxation of the single Thr718Ala mutation in human topoisomerase I: a functional and molecular dynamics study
    Giovanni Chillemi
    CASPUR Interuniversities Consortium for Supercomputing Applications Via dei Tizii 6b, Rome 00185, Italy
    Nucleic Acids Res 33:3339-50. 2005
    The 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...
  44. ncbi Human DNA topoisomerase I: relaxation, roles, and damage control
    John 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. 2005
    Human DNA topoisomerase I is an essential enzyme involved in resolving the torsional stress associated with DNA replication, transcription, and chromatin condensation...
  45. ncbi Poly(ADP-ribosyl)ation as a DNA damage-induced post-translational modification regulating poly(ADP-ribose) polymerase-1-topoisomerase I interaction
    Tetsu 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...
  46. ncbi Mutation at the catalytic site of topoisomerase I in CEM/C2, a human leukemia cell line resistant to camptothecin
    A 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...
  47. pmc DNA relaxation by human topoisomerase I occurs in the closed clamp conformation of the protein
    James 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. 2003
    In cocrystal structures of human topoisomerase I and DNA, the enzyme is tightly clamped around the DNA helix...
  48. pmc Rotation of DNA around intact strand in human topoisomerase I implies distinct mechanisms for positive and negative supercoil relaxation
    Levent 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 ..
  49. pmc 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 factor
    E 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. 1998
    Human 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...
  50. pmc The interaction between p53 and DNA topoisomerase I is regulated differently in cells with wild-type and mutant p53
    C 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. 1999
    DNA 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...
  51. pmc Interaction between the N-terminus of human topoisomerase I and SV40 large T antigen
    P 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. 1998
    We 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 ..
  52. ncbi Topoisomerase I and ATP activate cDNA synthesis of human immunodeficiency virus type 1
    Hidehiro 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. 2002
    Replication 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 ..
  53. pmc Interaction between human topoisomerase I and a novel RING finger/arginine-serine protein
    P 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. 1999
    The N-terminus of human topoisomerase I participates in the binding of this enzyme to helicases and other proteins...
  54. ncbi Monoclonal antibodies neutralizing mammalian DNA topoisomerase I activity
    P 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...
  55. pmc Poisoning of human DNA topoisomerase I by ecteinascidin 743, an anticancer drug that selectively alkylates DNA in the minor groove
    Y 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)...
  56. ncbi Ecteinascidin 743 induces protein-linked DNA breaks in human colon carcinoma HCT116 cells and is cytotoxic independently of topoisomerase I expression
    Y 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...
  57. ncbi Camptothecin sensitivity is mediated by the pleiotropic drug resistance network in yeast
    R J Reid
    Department of Biochemistry and Molecular Pharmacology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    J Biol Chem 272:12091-9. 1997
    The antineoplastic alkaloid camptothecin interferes with the catalytic cycle of DNA topoisomerase I rendering it a cellular poison...
  58. ncbi Two new flavonol glycosides as DNA topoisomerase I poisons
    M 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...
  59. pmc Mdr1/P-glycoprotein, topoisomerase, and glutathione-S-transferase pi gene expression in primary and relapsed state adult and childhood leukaemias
    V 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...
  60. ncbi Clinical pharmacokinetics of irinotecan
    G 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...
  61. ncbi An in vitro evaluation of human DNA topoisomerase I inhibition by Peganum harmala L. seeds extract and its beta-carboline alkaloids
    Armin 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...
  62. pmc Induction of neuronal apoptosis by camptothecin, an inhibitor of DNA topoisomerase-I: evidence for cell cycle-independent toxicity
    E 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...
  63. pmc Increased susceptibility of spinal muscular atrophy fibroblasts to camptothecin is p53-independent
    Chia 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...
  64. ncbi Synthesis of new indeno[1,2-c]isoquinolines: cytotoxic non-camptothecin topoisomerase I inhibitors
    M 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. 2000
    In 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 ..
  65. ncbi Cloning of Chinese hamster DNA topoisomerase I cDNA and identification of a single point mutation responsible for camptothecin resistance
    A 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...
  66. pmc SCT1 mutants suppress the camptothecin sensitivity of yeast cells expressing wild-type DNA topoisomerase I
    E 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. 1995
    Camptothecin 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...
  67. ncbi Novel missense mutation of the DNA topoisomerase I gene in SN-38-resistant DLD-1 cells
    Yasuhiro 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 ..
  68. pmc Nucleolar function and size in cancer cells
    M 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...
  69. ncbi Silatecan DB-67 is a novel DNA topoisomerase I-targeted radiation sensitizer
    Allan 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 ..
  70. ncbi The effects of camptothecin on RNA polymerase II transcription: roles of DNA topoisomerase I
    Giovanni Capranico
    Department of Biochemistry, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy
    Biochimie 89:482-9. 2007
    Eukaryotic DNA topoisomerase I is active in transcribed chromatin domains to modulate transcription-generated DNA torsional tension...
  71. ncbi Action models for the antitumor drug camptothecin: formation of alkali-labile complex with DNA and inhibition of human DNA topoisomerase I
    Sergei 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...
  72. ncbi Mutation of Gly721 alters DNA topoisomerase I active site architecture and sensitivity to camptothecin
    Marie van der Merwe
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    J Biol Chem 283:3305-15. 2008
    DNA topoisomerase I (Top1p) catalyzes the relaxation of supercoiled DNA via a concerted mechanism of DNA strand cleavage and religation...
  73. pmc 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 formation
    M 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 ..
  74. doi Dissecting the transcriptional functions of human DNA topoisomerase I by selective inhibitors: implications for physiological and therapeutic modulation of enzyme activity
    Giovanni Capranico
    G Moruzzi Department of Biochemistry, University of Bologna, Bologna, Italy
    Biochim Biophys Acta 1806:240-50. 2010
    Camptothecin is a selective inhibitor of DNA topoisomerase I, and has effective antitumor activity...
  75. ncbi Characterisation of two intronic nuclear-matrix-attachment regions in the human DNA topoisomerase I gene
    H Romig
    Department of Biology, University of Konstanz, Germany
    Eur J Biochem 221:411-9. 1994
    We identify two high-affinity matrix-attachment regions (MAR elements) located in two introns of the human DNA topoisomerase I gene (TOP1)...
  76. ncbi Differential poisoning of human and Aspergillus nidulans DNA topoisomerase I by bi- and terbenzimidazoles
    G H Goldman
    Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Brazil
    Biochemistry 36:6488-94. 1997
    DNA 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...
  77. ncbi The level of anti-topoisomerase I antibodies highly correlates with metacarpophalangeal and proximal interphalangeal joints flexion contractures in patients with systemic sclerosis
    M Radic
    Department of Internal Medicine, Clinical Hospital Split, Split, Croatia
    Clin Exp Rheumatol 24:407-12. 2006
    It 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.
  78. pmc Genome-wide analysis of novel splice variants induced by topoisomerase I poisoning shows preferential occurrence in genes encoding splicing factors
    Stéphanie 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...
  79. ncbi Nonclassic functions of human topoisomerase I: genome-wide and pharmacologic analyses
    Ze Hong Miao
    Laboratories of Molecular Pharmacology, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland, USA
    Cancer Res 67:8752-61. 2007
    The biological functions of nuclear topoisomerase I (Top1) have been difficult to study because knocking out TOP1 is lethal in metazoans...
  80. ncbi Clinical pharmacokinetics of topotecan
    V M Herben
    Department of Pharmacy and Pharmacology, Netherlands Cancer Institute, Amsterdam, The Netherlands
    Clin Pharmacokinet 31:85-102. 1996
    Topotecan (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 ..
  81. ncbi 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 enzyme
    Amit 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...
  82. ncbi Effect of some bis Mannich bases and corresponding piperidinols on DNA topoisomerase I
    Pakize 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...
  83. pmc Position-specific trapping of topoisomerase I-DNA cleavage complexes by intercalated benzo[a]- pyrene diol epoxide adducts at the 6-amino group of adenine
    Y 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. 2000
    DNA topoisomerase I (top1) is the target of potent anticancer agents, including camptothecins and DNA intercalators, which reversibly stabilize (trap) top1 catalytic intermediates (cleavage complexes)...
  84. ncbi The deubiquitinating enzyme Doa4p protects cells from DNA topoisomerase I poisons
    Paola Fiorani
    Department of Molecular Pharmacology, St Jude Children s Research Hospital, 332 N Lauderdale, Memphis, TN 38105, USA
    J Biol Chem 279:21271-81. 2004
    DNA 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)...
  85. pmc Analysis of DNA relaxation and cleavage activities of recombinant Mycobacterium tuberculosis DNA topoisomerase I from a new expression and purification protocol
    Thirunavukkarasu Annamalai
    Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York, USA
    BMC Biochem 10:18. 2009
    Mycobacterium 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...
  86. pmc Repair of topoisomerase I covalent complexes in the absence of the tyrosyl-DNA phosphodiesterase Tdp1
    Chunyan 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. 2002
    Accidental 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...
  87. ncbi Thermotoga maritima-Escherichia coli chimeric topoisomerases. Answers about involvement of the carboxyl-terminal domain in DNA topoisomerase I-mediated catalysis
    Thierry 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...
  88. pmc Pea DNA topoisomerase I is phosphorylated and stimulated by casein kinase 2 and protein kinase C
    Narendra 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. 2003
    DNA 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...
  89. pmc Therapeutic activity of CPT-11, a DNA-topoisomerase I inhibitor, against peripheral primitive neuroectodermal tumour and neuroblastoma xenografts
    G Vassal
    Department of Pediatric Oncology, Institut Gustave Roussy, Villejuif, France
    Br J Cancer 74:537-45. 1996
    The 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...
  90. ncbi Poly(ADPR)polymerase-1 signalling of the DNA damage induced by DNA topoisomerase I poison in D54(p53wt) and U251(p53mut) glioblastoma cell lines
    Gabriella 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...
  91. pmc Topoisomerase I-mediated DNA cleavage induced by the minor groove-directed binding of bibenzimidazoles to a distal site
    Qasim 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. 2007
    Many 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 ..
  92. pmc Targeting to transcriptionally active loci by the hydrophilic N-terminal domain of Drosophila DNA topoisomerase I
    W L Shaiu
    Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA
    Mol Cell Biol 18:4358-67. 1998
    DNA topoisomerase I (topo I) from Drosophila melanogaster contains a nonconserved, hydrophilic N-terminal domain of about 430 residues upstream of the conserved core domains...
  93. pmc Characterisation of a human small-cell lung cancer cell line resistant to the DNA topoisomerase I-directed drug topotecan
    M Sorensen
    Department of Pathology, Sundby Hospital, Copenhagen, Denmark
    Br J Cancer 72:399-404. 1995
    Camptothecins are DNA topoisomerase I-directed anti-tumour drugs with a novel mechanism of action...
  94. ncbi Chemotherapy with irinotecan (CPT-11), a topoisomerase-I inhibitor, for refractory and relapsed non-Hodgkin's lymphoma
    T 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...
  95. ncbi A quantitative RT-PCR method to determine topoisomerase I mRNA levels in human tissue samples
    Karine Durand-Faucher
    Department of Biochemistry and Molecular Genetics, CHU Dupuytren, Limoges, France
    Clin Chem Lab Med 43:707-14. 2005
    DNA topoisomerase I (Topo I) is involved in DNA replication, transcription, recombination and repair...
  96. ncbi Induction of radiosensitization by indolocarbazole derivatives: the role of DNA topoisomerase I
    Allan Y Chen
    Department of Radiation Oncology, UC Davis Medical Center, 4501 X Street, G 126, Sacramento, CA 95817, USA
    Mol Pharmacol 66:553-60. 2004
    DNA 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)...
  97. ncbi 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. 1999
    Mammalian DNA topoisomerase I is a multifunctional enzyme which is essential for embryonal development...
  98. ncbi 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 checkpoints
    Yves 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. 2004
    Camptothecins 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...
  99. pmc CDC45 and DPB11 are required for processive DNA replication and resistance to DNA topoisomerase I-mediated DNA damage
    R J Reid
    Department of Biochemistry, Thomas Jefferson University, Philadelphia, PA 19107, USA
    Proc Natl Acad Sci U S A 96:11440-5. 1999
    The antitumor agent camptothecin targets DNA topoisomerase I by reversibly stabilizing a covalent enzyme-DNA intermediate...
  100. pmc Reduced expression of DNA topoisomerase I in SF295 human glioblastoma cells selected for resistance to homocamptothecin and diflomotecan
    ZhiYong Liao
    Laboratory of Molecular Pharmacology, Bldg, 37, Rm 5068, National Institutes of Health, Bethesda, MD 20892 4255, USA
    Mol Pharmacol 73:490-7. 2008
    Homocamptothecins (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...

Research Grants66

  1. TOPOISOMERASE I AS AN ANTITUMOR DRUG TARGET
    PETER D ARPA; Fiscal Year: 2003
    ..The proposed research focuses on the molecular responses to camptothecin-DNA-topoisomerase I complexes...
  2. DNA TOPOISOMERASE-CAMPTOTHECIN INTERACTIONS
    Mary Ann Bjornsti; Fiscal Year: 2007
    DNA 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...
  3. SAR OF NOVEL TOPO I INHIBITOR AGAINST PROSTATE CANCER
    YUE 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...
  4. Benzo[i]phenanthridines: TOP1-Targeting Antitumor Agents
    EDMOND LAVOIE; Fiscal Year: 2006
    b>Topoisomerase I (TOP1) is an enzyme that alters the topology of DNA by transiently breaking one DNA strand...
  5. Novel Mechanisms by which RAD18 and POLZ affect Response to Anticancer Agents
    CHRISTINE ELIZABETH CANMAN; Fiscal Year: 2010
    Drugs which target DNA through direct crosslinking or trapping of topoisomerase I (TOP1) complexes are some of the most effective treatments for cancer...
  6. VACCINIA VIRUS DNA TOPOISOMERASE I
    Stewart 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...
  7. DNA TOPOISOMERASE-CAMPTOTHECIN INTERACTIONS
    Mary Ann Bjornsti; Fiscal Year: 2010
    DNA 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...
  8. MECHANISMS OF SUPPRESSING CAMPTOTHECIN TOXICITY
    Mary Ann Bjornsti; Fiscal Year: 2003
    DESCRIPTION: (Applicant's Abstract) In recent years, DNA topoisomerase I (Top1) has emerged as the cellular target of an increasing number of antitumor agents...
  9. DNA Topoisomerase Camptothecin Interactions
    Mary Ann Bjornsti; Fiscal Year: 2005
    DESCRIPTION (PROVIDED BY APPLICANT): DNA topoisomerase I (Top1p) plays an important role in DNA replication, transcription and recombination...
  10. SUMOylation and Cell Sensitivity to Top1 Poisons
    Mary Ann Bjornsti; Fiscal Year: 2009
    Eukaryotic 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...
  11. DNA TOPOISOMERASE I TARGET INTERACTIONS OF CAMPTOTHECINS
    Danzhou 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...
  12. MECHANISM OF ACTION OF ANTITUMOR DRUGS
    Leroy F Liu; Fiscal Year: 2010
    The long-term goal of this application is to understand the mechanism of action of topoisomerase I (Top1)-targeting drugs. Camptothecins (CPTs) (e.g...
  13. Topoisomerase I-directed Anticancer Drugs
    Leroy Liu; Fiscal Year: 2004
    Human DNA topoisomerase I (hTOP1) is a highly effective new molecular target for anticancer drugs such as camptothecins (CPTs). CPTs inhibit (poison) TOP1 by trapping a covalent reaction intermediate, the ternary TOP1 cleavable complex...