topoisomerase I

Summary

Gene Symbol: topoisomerase I
Description: topoisomerase (DNA) I
Alias: TOPI, 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. 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
  5. 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
  6. pmc Replacement of the human topoisomerase linker domain with the plasmodial counterpart renders the enzyme camptothecin resistant
    Barbara Arnò
    Department of Biology and Interuniversity Consortium, National Institute Biostructure and Biosystem, University of Rome Tor Vergata, Rome, Italy
    PLoS ONE 8:e68404. 2013
  7. doi TOP1 gene copy numbers in colorectal cancer samples and cell lines and their association to in vitro drug sensitivity
    Maria Unni Rømer
    Department of Veterinary Disease Biology, Section of Pathobiology, Faculty of Life Sciences, University of Copenhagen, Frederiksberg C, Denmark
    Scand J Gastroenterol 47:68-79. 2012
  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. 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
  10. 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

Detail Information

Publications205 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. 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...
  5. 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
    ..Moreover, this demonstration is the first that shows the specific oxidation of an autoantigen directly participates in the pathogenesis of an autoimmune disease...
  6. pmc Replacement of the human topoisomerase linker domain with the plasmodial counterpart renders the enzyme camptothecin resistant
    Barbara Arnò
    Department of Biology and Interuniversity Consortium, National Institute Biostructure and Biosystem, University of Rome Tor Vergata, Rome, Italy
    PLoS ONE 8:e68404. 2013
    ....
  7. doi TOP1 gene copy numbers in colorectal cancer samples and cell lines and their association to in vitro drug sensitivity
    Maria Unni Rømer
    Department of Veterinary Disease Biology, Section of Pathobiology, Faculty of Life Sciences, University of Copenhagen, Frederiksberg C, Denmark
    Scand J Gastroenterol 47:68-79. 2012
    ..In this study, we analyzed TOP1 gene copy number variation in tumor tissue from CRC patients and CRC cell lines with different sensitivities to the TOP1 inhibitor SN-38 and oxaliplatin...
  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. 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...
  10. 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)...
  11. 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...
  12. doi The human topoisomerase 1B Arg634Ala mutation results in camptothecin resistance and loss of inter-domain motion correlation
    Ilda D'Annessa
    Department of Biology and Interuniversity Consortium, National Institute Biostructure and Biosystem INBB, University of Rome Tor Vergata, Via della Ricerca Scientifica, Rome 00133, Italy
    Biochim Biophys Acta 1834:2712-21. 2013
    ..These results indicate that the loss of motion correlation and the drug resistance are two strongly correlated events. ..
  13. pmc Mutational analysis of the preferential binding of human topoisomerase I to supercoiled DNA
    Zheng Yang
    Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195 7242, USA
    FEBS J 276:5906-19. 2009
    Human topoisomerase I binds DNA in a topology-dependent fashion with a strong preference for supercoiled DNAs of either sign over relaxed circular DNA...
  14. 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...
  15. 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...
  16. 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...
  17. 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...
  18. pmc A ubiquitin-proteasome pathway for the repair of topoisomerase I-DNA covalent complexes
    Chao Po Lin
    Department of Pharmacology, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA
    J Biol Chem 283:21074-83. 2008
    Reversible topoisomerase I (Top1)-DNA cleavage complexes are the key DNA lesion induced by anticancer camptothecins (e.g. topotecan and irinotecan) as well as structurally perturbed DNAs (e.g...
  19. 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...
  20. 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...
  21. 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)...
  22. 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...
  23. pmc New Topoisomerase I mutations are associated with resistance to camptothecin
    Celine Gongora
    Institut de Recherche en Cancérologie de Montpellier, INSERM, Université Montpellier1, CRLC Val d Aurelle Paul Lamarque, Montpellier, France
    Mol Cancer 10:64. 2011
    b>Topoisomerase I (TOP1) is a nuclear enzyme that catalyzes the relaxation of supercoiled DNA during DNA replication and transcription...
  24. doi Topoisomerase I amplification in melanoma is associated with more advanced tumours and poor prognosis
    Denise Ryan
    UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin, Ireland
    Pigment Cell Melanoma Res 23:542-53. 2010
    ..These observations open the possibility that TOP1-targeted therapeutics may be of benefit in a particular subgroup of advanced stage melanoma patients...
  25. ncbi Betulinic acid, a catalytic inhibitor of topoisomerase I, inhibits reactive oxygen species-mediated apoptotic topoisomerase I-DNA cleavable complex formation in prostate cancer cells but does not affect the process of cell death
    Agneyo Ganguly
    Molecular Parasitology Laboratory, Indian Institute of Chemical Biology, Kolkata, India
    Cancer Res 67:11848-58. 2007
    The ubiquitious enzyme topoisomerase I can be targeted by drugs which turn these enzymes into cellular poisons and subsequently induce cell death...
  26. pmc Thr729 in human topoisomerase I modulates anti-cancer drug resistance by altering protein domain communications as suggested by molecular dynamics simulations
    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 36:5645-51. 2008
    The role of Thr729 in modulating the enzymatic function of human topoisomerase I has been characterized by molecular dynamics (MD) simulation...
  27. 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...
  28. pmc Proteasome-dependent processing of topoisomerase I-DNA adducts into DNA double strand breaks at arrested replication forks
    Chao Po Lin
    Department of Pharmacology, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, Piscataway, New Jersey 08854 5635, USA
    J Biol Chem 284:28084-92. 2009
    Reversible topoisomerase I (Top1)-DNA cleavage complexes are the key DNA lesion induced by anticancer camptothecins (CPTs) (e.g. topotecan and irinotecan) as well as structurally perturbed DNAs (e.g...
  29. 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...
  30. 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...
  31. 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...
  32. 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...
  33. 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...
  34. 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...
  35. 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)...
  36. 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...
  37. 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...
  38. 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...
  39. 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 ..
  40. 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...
  41. 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 ..
  42. 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 ..
  43. 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...
  44. ncbi Proteomic analysis of complexes formed by human topoisomerase I
    Alicja Czubaty
    Institute of Biochemistry, Warsaw University, ul Miecznikowa 1, 02 096 Warszawa, Poland
    Biochim Biophys Acta 1749:133-41. 2005
    Human topoisomerase I is a nuclear enzyme that catalyses DNA relaxation and phosphorylation of SR proteins. Topoisomerase I participates in several protein-protein interactions...
  45. 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...
  46. 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...
  47. 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...
  48. 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...
  49. 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...
  50. 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-..
  51. 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...
  52. 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...
  53. doi Native state dynamics and mechanical properties of human topoisomerase I within a structure-based coarse-grained model
    Oliwia Szklarczyk
    Department of Computer Science, Institute of Theoretical Computer Science, ETH Zurich, Zurich, Switzerland
    Proteins 77:420-31. 2009
    ..A coarse grained molecular dynamics model with an implicit solvent is used to elucidate properties of the human topoisomerase I. The model is defined through the native structure and it allows covering significantly longer time scales ..
  54. ncbi RRM proteins interacting with the cap region of topoisomerase I
    Agata M Trzcinska-Daneluti
    Institute of Biochemistry, Faculty of Biology, Warsaw University, Miecznikowa 1, 02 096 Warsaw, Poland
    J Mol Biol 369:1098-112. 2007
    ..two closely spaced RRM domains were previously found in protein complexes formed by the cap region of human topoisomerase I, a nuclear enzyme responsible for DNA relaxation or phosphorylation of SR splicing proteins...
  55. 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...
  56. 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 ..
  57. doi Identification of a minimal functional linker in human topoisomerase I by domain swapping with Cre recombinase
    Rikke From Frøhlich
    Department of Molecular Biology and Interdisciplinary Nanoscience Center iNANO, University of Aarhus, Denmark
    Biochemistry 47:7127-36. 2008
    ..this study we replace 86 amino acids including the linker domain of the cellular type IB topoisomerase, human topoisomerase I, with four, six, or eight amino acids from the corresponding short loop region in Cre recombinase...
  58. ncbi The role of lysine 532 in the catalytic mechanism of human topoisomerase I
    Heidrun Interthal
    Department of Microbiology, University of Washington School of Medicine, Seattle, Washington 98195 7242, USA
    J Biol Chem 279:2984-92. 2004
    Based on co-crystal structures of human topoisomerase I with bound DNA, Lys(532) makes a minor groove contact with the strongly preferred thymidine residue at the site of covalent attachment (-1 position)...
  59. ncbi Modulation of DNA topoisomerase I activity by p53
    C Gobert
    Rhone Poulenc Rorer SA, Centre de Recherche de Vitry Alfortville, Vitry sur Seine, France
    Biochemistry 35:5778-86. 1996
    ..We here show that mitomycin C treatment of human MCF7 breast adenocarcinoma cells results in increased topoisomerase I activity as measured by relaxation of supercoiled DNA and by phosphorylation of SR protein splicing factor...
  60. doi Erybraedin C, a natural compound from the plant Bituminaria bituminosa, inhibits both the cleavage and religation activities of human topoisomerase I
    Cinzia Tesauro
    CNR National Research Council, INFM National Institute for Physics of Matter, CNISM and Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, Rome 00133, Italy
    Biochem J 425:531-9. 2010
    The interaction of human topoisomerase I and erybraedin C, a pterocarpan purified from the plant Bituminaria bituminosa, that was shown to have an antitumour activity, was investigated through enzymatic activity assays and molecular ..
  61. 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...
  62. 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...
  63. ncbi Inhibition of topoisomerase I cleavage activity by thiol-reactive compounds: importance of vicinal cysteines 504 and 505
    Danièle Montaudon
    Groupe de Pharmacologie Moléculaire INSERM E347 and Institut Bergonié, 229 Cours de l Argonne, Université Victor Segalen Bordeaux II, 146 rue Leo Saignat, 33076 Bordeaux Cedex, France
    J Biol Chem 282:14403-12. 2007
    DNA topoisomerase I (Top1) is a nuclear enzyme that plays a crucial role in the removal of DNA supercoiling associated with replication and transcription. It is also the target of the anticancer agent, camptothecin (CPT)...
  64. 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...
  65. ncbi Assembly of a polymeric chain of SUMO1 on human topoisomerase I in vitro
    Meiluen Yang
    Institute of Biochemistry and Molecular Biology, School of Life Science, National Yang Ming University, Taipei 112, Taiwan
    J Biol Chem 281:8264-74. 2006
    Human (h) DNA topoisomerase I has been identified as a major SUMO1 target in camptothecin-treated cells...
  66. ncbi Heterozygous disruption of the DNA topoisomerase I gene confers cellular resistance to camptothecin in human cells
    Eriko Toyoda
    International Graduate School of Arts and Sciences, Yokohama City University, Japan
    Biol Pharm Bull 32:724-7. 2009
    DNA topoisomerase I (Top1) is a ubiquitous nuclear enzyme that plays essential roles in various cellular processes, such as transcription or replication...
  67. 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...
  68. 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...
  69. 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 ..
  70. 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...
  71. 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 ..
  72. 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 ..
  73. 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...
  74. 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...
  75. 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)...
  76. 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...
  77. 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...
  78. 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...
  79. 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...
  80. 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...
  81. 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...
  82. 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...
  83. 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...
  84. 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 ..
  85. 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...
  86. 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...
  87. 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 ..
  88. 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...
  89. 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 ..
  90. 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...
  91. 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...
  92. 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...
  93. 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)...
  94. 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 ..
  95. 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...
  96. 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...
  97. 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.
  98. 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...
  99. 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...
  100. 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 ..

Research Grants58

  1. Ras18-mediated Fanconi Anemia pathway activation in response to camptothecin
    Komaraiah Palle; Fiscal Year: 2013
    ..term goal of this proposal is to understand the molecular mechanisms that repair DNA damage induced by DNA topoisomerase I (Top1) -targeting anticancer drugs such as camptothecin (CPT) and its analogues...
  2. Novel Topoisomerase I Inhibitors
    MARK S CUSHMAN; Fiscal Year: 2013
    ..provided by applicant): The long-term goals of this project are to design, synthesize and evaluate novel topoisomerase I (Top1) inhibitors for the treatment of cancer...
  3. Novel Mechanisms by which RAD18 and POLZ affect Response to Anticancer Agents
    CHRISTINE ELIZABETH CANMAN; Fiscal Year: 2012
    DESCRIPTION (provided by applicant): Drugs which target DNA through direct crosslinking or trapping of topoisomerase I (TOP1) complexes are some of the most effective treatments for cancer...
  4. Tumorigenic Role of the CUL4A Ubiquitin Ligase
    Pengbo Zhou; Fiscal Year: 2013
    ..development and maintenance;(2) Delineate the mechanistic role of CUL4 dysregulation in tumor resistance to topoisomerase I inhibitor chemotherapy drugs...
  5. Optimization of dipeptide-linked benzimidazole topoisomerase 1 poisons
    Craig Beeson; Fiscal Year: 2009
    Derivatives of camptothecin (CPT) that inhibit Topoisomerase I (Top1) activity have demonstrated clinical utility in the treatment of various cancers...
  6. Benzo[i]phenanthridines: TOP1-Targeting Antitumor Agents
    EDMOND LAVOIE; Fiscal Year: 2006
    unreadable] DESCRIPTION (provided by applicant): Topoisomerase I (TOP1) is an enzyme that alters the topology of DNA by transiently breaking one DNA strand...
  7. TOPOISOMERASE I STRUCTURE AND REGULATION
    Eric Rubin; Fiscal Year: 1999
    This proposal is designed to enhance the current understanding of the interaction between DNA topoisomerase I and inhibitory antineoplastic drugs...
  8. 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...
  9. 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...
  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: 2013
    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. CONTROL OF DNA TOPOLOGY
    Yuk Ching Tse-Dinh; Fiscal Year: 2013
    ..Previous results have shown that accumulation of type IA topoisomerase I cleavage complex can trigger bacterial cell death but specific inhibitors of type IA bacterial topoisomerase ..
  14. MUTATIONAL ANALYSIS OF E COLI DNA TOPOISOMERASE III
    Russell DiGate; Fiscal Year: 2005
    ..The type I enzymes can be further subdivided into type IA prokaryotic DNA topoisomerase I (Topo I) and III (Topo III), and eukaryotic DNA topoisomerase III (Topo III)) and type IB (eukaryotic DNA ..
  15. Novel Camptothecins with DNA Binding Activity
    Li ming Zhou; Fiscal Year: 2001
    ..Extensive investigations on CPTs, specific topoisomerase I inhibitors, have led to the FDA approval of two water-soluble derivatives of CPT...
  16. Potentiation of Topoisomerase I Inhibitors
    Jing Zhen Deng; Fiscal Year: 2002
    ..goal of this SBIR is the identification of small molecules that can reinforce the antitumor activity of DNA topoisomerase I inhibitors by acting at a biochemical locus linked functionally to topoisomerase I...
  17. HUMAN TOPO I--AN EXPLOITABLE ANTICANCER DRUG TARGET
    James Abbruzzese; Fiscal Year: 1992
    ..on the general biochemical principles to be employed, the approach developed in this trial will be applicable to subsequent Phase II trials of hycamptamine and to the development of other inhibitors of human DNA topoisomerase I and II.
  18. Topoisomerase 1 and mutagenesis in yeast
    Sue Jinks-Robertson; Fiscal Year: 2013
    ..Given the universality of DNA structure and basic DNA metabolic processes, results in the yeast system will be relevant to issues of genome stability in higher eukaryotes. ..
  19. DNA Minor Groove-Targeting Anticancer Agents
    DANIEL PILCH; Fiscal Year: 2006
    ..The information gleaned from our proposed studies will enable us to develop a rational approach to the design and development of next generation TB compounds that exhibit predictably enhanced TOP1 poisoning and cytotoxic activities. ..
  20. DRUG SEQUENCING RESISTANCE IN MULTIPLE MYELOMA
    Daniel Sullivan; Fiscal Year: 1999
    ..The second major hypothesis of this application is that alterations in topoisomerase I and II (content, location and activity) are involved in the drug resistance of myeloma cells in vivo...
  21. Chemical Glycobiology on Anthracyclines
    Peng Wang; Fiscal Year: 2009
    ..The success of such a platform will accelerate new drug discovery in the field of anticancer drug involving DNA-enzyme-drug complex. This research program should produce new generations of preclinical anthracycline drug candidates. ..
  22. Topoisomerase-Associated Genome Instability
    SABRINA COTE; Fiscal Year: 2013
    ..I'm using high-throughput sequencing and SNP microarrays to fine map and characterize the recombination events. The project will also be extended into mammalian cells on a limited basis. ..
  23. MECHANISMS OF ACTION AND RESISTANCE TO ICRF187
    Jack Yalowich; Fiscal Year: 2000
    ..3. test the hypothesis that ICRF-187 inhibition of topo II will upregulate DNA topoisomerase I levels and sensitize cells to inhibitors such as topotecan...
  24. Translation of Novel Therapeutic Targets in Multiple Myeloma
    ALEXANDER KEITH STEWART; Fiscal Year: 2013
    ....
  25. T Cells in the Pathogenesis of Systemic Sclerosis
    Chris Platsoucas; Fiscal Year: 2005
    ..by limiting dilution T-cell clones specific for alloantigens or for putative SSc antigens (CMV and DNA topoisomerase I) from the same SSc patients studied in specific aim #1. a...
  26. FOURTH CONFERENCE ON DNA TOPOISOMERASES IN THERAPY
    Milan Potmesil; Fiscal Year: 1992
    ..The conference will discuss not only anticancer agents and their target DNA topoisomerase I or II, but also a closely related enzyme DNA gyrase targeted by quinolones and related drugs...
  27. VASCULOPATHY, APOPTOSIS AND AUTOIMMUNITY
    JOSEPH AHEARN; Fiscal Year: 2003
    ..generated by patients with systemic sclerosis are uniquely targeted to nucleolar proteins such as DNA topoisomerase I (topo-I)...
  28. Instability of Triplet Repeats in Mammalian Cells
    Leroy Hubert; Fiscal Year: 2009
    ..Specific Aim 2: Determine the roles of Topi and Tdp1 in TNR instability...
  29. GENETIC CONTROL OF MAMMALIAN CELL SURFACE FUNCTIONS
    Nobuyoshi Shimizu; Fiscal Year: 1993
    ..4. Activation of DNA topoisomerase I (Topo I) by protein kinase C-mediated phosphorylation as a significant nuclear event of signal transduction...
  30. EXPLORING THE INTERACTION BETWEEN SGS1 AND TOP3
    Marisa Wagner; Fiscal Year: 2004
    ..The goal of this proposal is to investigate the functions of Sgs1 and Top3 in S. cerevisiae using combined genetic, biochemical, and cell biological approaches. ..
  31. Regulation of SPARC in Scleroderma Fibroblasts
    Xiaodong Zhou; Fiscal Year: 2007
    ..In addition, we will investigate whether exogenous SPARC can restore or increase fibrogenic effects of TGF-beta on cultured fibroblasts with or without suppression of the SPARC gene using recombinent SPARC protein. ..
  32. Replication Protein A and the DNA Damage response
    Steven Brill; Fiscal Year: 2006
    ..These studies will provide insight into the nature of the DNA damage signal and the regulation of checkpoint kinases. The results are expected to have broad implications for the mechanism of DNA repair in human cells. ..
  33. DNA REPAIR AND ANTITOPOISOMERASE DRUG EFFECTS
    John L Nitiss; Fiscal Year: 2010
    ..Answering these questions may also suggest strategies for circumventing resistance to these clinically important anticancer drugs. ..
  34. Studies of a Novel Therapeutic Target in Non-Small Cell Lung Cancer (NSCLC)
    Ravi Salgia; Fiscal Year: 2011
    ..Conduct an anti-c-Met phase I/I I clinical trial against NSCLC. Through the achievement of the goals proposed in these specific aims, we will arrive at novel therapy against c- Met in lung cancer. ..
  35. 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...
  36. Molecular Determinants of Mitochondrial Optic Atrophy
    SUSAN CLINE; Fiscal Year: 2005
    ..abstract_text> ..
  37. GENOMIC STABILITY AND AGING IN YEAST
    Steven Brill; Fiscal Year: 2003
    ..abstract_text> ..
  38. MECHANISM AND INHIBITION OF HUMAN DNA TOPOISOMERASE I
    SIDNEY HECHT; Fiscal Year: 2003
    The long term goals of this research are characterization of the nature of DNA relaxation by eukaryotic DNA topoisomerase I at a molecular level and identification of those parameters of topoisomerase I inhibition that are critical for ..
  39. FUNCTIONAL AND MECHANISTIC STUDIES OF DNA TOPOISOMERASES
    Leroy Liu; Fiscal Year: 2001
    ..We will also determine which TOP2 isoform is responsible for HMW DNA fragmentation during apoptotic cell death. ..
  40. MECHANISM OF INDUCTION OF MALIGNANT GLIOMAS
    Demetrius Kokkinakis; Fiscal Year: 2002
    ..Genetic differences between tumor cells and those capable of infiltrating the normal parenchyma will also be identified and compared to those of initiated multipotent progenitor cells in order to understand their lineage. ..
  41. Structure and Mechanism of Human Topoisomerase I
    MATTHEW REDINBO; Fiscal Year: 2004
    Description (applicant's description): Human topoisomerase I plays a critical role in nearly every cellular process involving DNA, including replication, transcription and recombination...
  42. Identification of Green Tea Polyphenol-Targeted Genes
    Stephen Hsu; Fiscal Year: 2004
    ..Data generated from this proposal may reveal novel drug targets for treatment of head and neck cancer. ..
  43. NATURAL PRODUCTS DISCOVERY - NUCLEAR AND SIGNALING TARGE
    SIDNEY HECHT; Fiscal Year: 2004
    ..validated assay to guide the screening/isolation of novel DNA damaging agents, and inhibitors of DNA topoisomerase I, DNA topoisomerase II, DNA polymerase B and Myt1 kinase (Programs 1, 2 and 3) 2...
  44. Recombination-mediated DNA repair in yeast
    Steven Brill; Fiscal Year: 2006
    ..It is expected that the results of these experiments will shed light on the nature of replication fork arrest and the mechanism of recombination-mediated DNA repair in eukaryotes. ..
  45. Identification of Anti-Viral Compounds from Plants
    Shiyou Li; Fiscal Year: 2005
    ..abstract_text> ..
  46. Structure and Function of the Human Pregnane X Receptor
    MATTHEW REDINBO; Fiscal Year: 2006
    ..5. Elucidate structures of hPXR in complexes with large drugs like rifampicin and taxol. 6. Examine structures of mouse and rabbit PXR to determine why different species respond to distinct xenobiotics. ..
  47. INTERACTION OF BLEOMYCIN WITH RNA AND DNA
    SIDNEY HECHT; Fiscal Year: 2006
    ..In spite of the obvious utility and importance of the bleomycins as antitumor agents, there are clear opportunities to alter the molecular behavior of bleomycin, and thereby potentially improve its antitumor efficacy. ..
  48. ELABORATION OF MODIFIED PROTEINS USING MISACYLATED TRNAS
    SIDNEY HECHT; Fiscal Year: 2007
    ..Also of interest is the exploitation of a new method for introducing a broader range of amino acid analogues into the derived proteins, and the elaboration of the modified proteins in an intact cellular system ..
  49. SYNTHESIS OF BLEOMYCIN GROUP ANTIBIOTICS AND ANALOGUES
    SIDNEY HECHT; Fiscal Year: 2007
    ..These libraries will be used to select BLMs having specific desirable properties and the identified analogues will be characterized thoroughly as potential anti-tumor agents. ..
  50. LIGANDS FOR PROBING THE ACTIVE SITE OF LUMAZINE SYNTHASE
    Mark Cushman; Fiscal Year: 2008
    ..abstract_text> ..
  51. Transcription-associated mutations
    MALCOLM LIPPERT; Fiscal Year: 2008
    ..The work proposed here will clarify the breadth of TAM and begin to identify its underlying mechanism(s) - critical steps toward understanding its overall influence on human health. [unreadable] [unreadable] [unreadable]..
  52. Development of a HTS system:topoisomerase targets (RMI)
    Yuk Ching Tse Dinh; Fiscal Year: 2004
    ..positive and negative supercoils in DNA is a major function of topoisomerases, including poxvirus topoisomerase I. The trapping of covalent intermediates complexed with cleaved DNA formed by topoisomerases during removal of ..
  53. Synthesis of New NNRTLs for the Treatment of AIDS
    Mark Cushman; Fiscal Year: 2005
    ..The activities of the ADAMs vs. NNRTI resistant viruses will be investigated. The aqueous solubilities of the new ADAMs will be measured accurately. ..