dna topoisomerases

Summary

Summary: Enzymes that regulate the topology of DNA by actions such as breaking, relaxing, passing, and rejoining strands of DNA in cells. These enzymes are important components of the DNA replication system. They are classified by their substrate specificities. DNA TOPOISOMERASE I enzymes act on a single strand of DNA. DNA TOPOISOMERASE II enzymes act on double strands of DNA.

Top Publications

  1. ncbi DNA topoisomerases and their poisoning by anticancer and antibacterial drugs
    Yves Pommier
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 4255, USA
    Chem Biol 17:421-33. 2010
  2. ncbi DNA topoisomerases: harnessing and constraining energy to govern chromosome topology
    Allyn J Schoeffler
    Department of Molecular and Cell Biology, California Institute for Quantitative Biology, University of California Berkeley, Berkeley, CA, USA
    Q Rev Biophys 41:41-101. 2008
  3. ncbi DNA topoisomerases: structure, function, and mechanism
    J J Champoux
    Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington 98195 7242, USA
    Annu Rev Biochem 70:369-413. 2001
  4. pmc RDH54, a RAD54 homologue in Saccharomyces cerevisiae, is required for mitotic diploid-specific recombination and repair and for meiosis
    H L Klein
    Department of Biochemistry and Kaplan Cancer Center, New York University Medical Center, New York 10016, USA
    Genetics 147:1533-43. 1997
  5. pmc Characterization of the roles of the Saccharomyces cerevisiae RAD54 gene and a homologue of RAD54, RDH54/TID1, in mitosis and meiosis
    M Shinohara
    Department of Biology, Graduate School of Science, Osaka University, Toyonaka, Japan
    Genetics 147:1545-56. 1997
  6. pmc Phylogenomics of DNA topoisomerases: their origin and putative roles in the emergence of modern organisms
    Patrick Forterre
    Institut de Genetique et Microbiologie, Univ Paris Sud, 91405 Orsay Cedex, France
    Nucleic Acids Res 37:679-92. 2009
  7. pmc Tid1/Rdh54 promotes colocalization of rad51 and dmc1 during meiotic recombination
    M Shinohara
    Department of Biology, Graduate School of Science, Osaka University, 1 1 Machikaneyma, Toyonaka, Osaka 560 0043, Japan
    Proc Natl Acad Sci U S A 97:10814-9. 2000
  8. pmc Swi2/Snf2-related translocases prevent accumulation of toxic Rad51 complexes during mitotic growth
    Parisha P Shah
    Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL 60637, USA
    Mol Cell 39:862-72. 2010
  9. pmc Nonoptimal DNA topoisomerases allow maintenance of supercoiling levels and improve fitness of Streptococcus pneumoniae
    Luz Balsalobre
    Unidad de Genetica Bacteriana, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Carretera a Pozuelo Km 2, 28220 Majadahonda, Madrid, Spain
    Antimicrob Agents Chemother 55:1097-105. 2011
  10. ncbi Flavonoids acting on DNA topoisomerases: recent advances and future perspectives in cancer therapy
    P Russo
    Laboratory of Systems Approaches and Non Communicable Diseases, IRCCS San Raffaele Pisana, Via di Valcannuta, 247, I 00166 Roma, Italia
    Curr Med Chem 19:5287-93. 2012

Research Grants

  1. FUNCTION AND BIOLOGY OF EUKARYOTIC DNA TOPOISOMERASES
    Neil Osheroff; Fiscal Year: 2013
  2. CONTROL OF DNA TOPOLOGY
    Yuk Ching Tse-Dinh; Fiscal Year: 2013
  3. Topoisomerases: Target for Antitrypanosomal Therapy
    Theresa Shapiro; Fiscal Year: 2009
  4. ANTI-TOPOISOMERASE DRUG ACTION IN YEAST
    John L Nitiss; Fiscal Year: 2013
  5. Structural studies of type I topoisomerases
    ALFONSO MONDRAGON; Fiscal Year: 2013
  6. DRUG SEQUENCING RESISTANCE IN MULTIPLE MYELOMA
    Daniel Sullivan; Fiscal Year: 1999
  7. DICATIONIC DRUGS--METABOLISM AND TOXICITY
    Richard Tidwell; Fiscal Year: 1993
  8. DNA TOPOISOMERASES--BIOLOGICAL FUNCTIONS AND MECHANISMS
    James Wang; Fiscal Year: 1999
  9. HPV DNA REPLICATION: NOVEL HOST FACTORS
    Thomas Melendy; Fiscal Year: 2003
  10. Top3 Homologues in Lymphocyte Genome Stability and Aging
    ALBERT SHAW; Fiscal Year: 2009

Detail Information

Publications238 found, 100 shown here

  1. ncbi DNA topoisomerases and their poisoning by anticancer and antibacterial drugs
    Yves Pommier
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 4255, USA
    Chem Biol 17:421-33. 2010
    b>DNA topoisomerases are the targets of important anticancer and antibacterial drugs...
  2. ncbi DNA topoisomerases: harnessing and constraining energy to govern chromosome topology
    Allyn J Schoeffler
    Department of Molecular and Cell Biology, California Institute for Quantitative Biology, University of California Berkeley, Berkeley, CA, USA
    Q Rev Biophys 41:41-101. 2008
    b>DNA topoisomerases are a diverse set of essential enzymes responsible for maintaining chromosomes in an appropriate topological state...
  3. ncbi DNA topoisomerases: structure, function, and mechanism
    J J Champoux
    Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington 98195 7242, USA
    Annu Rev Biochem 70:369-413. 2001
    b>DNA topoisomerases solve the topological problems associated with DNA replication, transcription, recombination, and chromatin remodeling by introducing temporary single- or double-strand breaks in the DNA...
  4. pmc RDH54, a RAD54 homologue in Saccharomyces cerevisiae, is required for mitotic diploid-specific recombination and repair and for meiosis
    H L Klein
    Department of Biochemistry and Kaplan Cancer Center, New York University Medical Center, New York 10016, USA
    Genetics 147:1533-43. 1997
    ..The RDH54 gene is also required for meiosis as homozygous mutant diploids show very poor sporulation and reduced spore viability. The role of the RDH54 gene in mitotic repair and in meiosis and the pathway in which it acts are discussed...
  5. pmc Characterization of the roles of the Saccharomyces cerevisiae RAD54 gene and a homologue of RAD54, RDH54/TID1, in mitosis and meiosis
    M Shinohara
    Department of Biology, Graduate School of Science, Osaka University, Toyonaka, Japan
    Genetics 147:1545-56. 1997
    ..These results suggest that one of the differences between the late stages of mitotic recombination and meiotic recombination might be specified by differential dependency on the Rad54 and Rdh54/Tid1 proteins...
  6. pmc Phylogenomics of DNA topoisomerases: their origin and putative roles in the emergence of modern organisms
    Patrick Forterre
    Institut de Genetique et Microbiologie, Univ Paris Sud, 91405 Orsay Cedex, France
    Nucleic Acids Res 37:679-92. 2009
    ..We also proposed that topoisomerases have played a critical role in the origin of modern genomes and in the emergence of the three cellular domains...
  7. pmc Tid1/Rdh54 promotes colocalization of rad51 and dmc1 during meiotic recombination
    M Shinohara
    Department of Biology, Graduate School of Science, Osaka University, 1 1 Machikaneyma, Toyonaka, Osaka 560 0043, Japan
    Proc Natl Acad Sci U S A 97:10814-9. 2000
    ....
  8. pmc Swi2/Snf2-related translocases prevent accumulation of toxic Rad51 complexes during mitotic growth
    Parisha P Shah
    Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL 60637, USA
    Mol Cell 39:862-72. 2010
    ....
  9. pmc Nonoptimal DNA topoisomerases allow maintenance of supercoiling levels and improve fitness of Streptococcus pneumoniae
    Luz Balsalobre
    Unidad de Genetica Bacteriana, Centro Nacional de Microbiologia, Instituto de Salud Carlos III, Carretera a Pozuelo Km 2, 28220 Majadahonda, Madrid, Spain
    Antimicrob Agents Chemother 55:1097-105. 2011
    ..An increase in the incidence of fluoroquinolone resistance, even in the absence of further antibiotic exposure, is envisaged...
  10. ncbi Flavonoids acting on DNA topoisomerases: recent advances and future perspectives in cancer therapy
    P Russo
    Laboratory of Systems Approaches and Non Communicable Diseases, IRCCS San Raffaele Pisana, Via di Valcannuta, 247, I 00166 Roma, Italia
    Curr Med Chem 19:5287-93. 2012
    ..Daidzein or its synthetic derivative Phenoxodiol as well as Luteolin and Quercetin are able to inhibit DNA topoisomerases. This review discusses that Flavonoids targeting DNA topoisomerases may lead to novel drug development with ..
  11. pmc A role for RAD54B in homologous recombination in human cells
    Kiyoshi Miyagawa
    Department of Molecular Pathology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1 2 3 Kasumi, Minami Ku, Hiroshima 734 8553, Japan
    EMBO J 21:175-80. 2002
    ..Our findings provide the first genetic evidence that the mitotic recombination pathway is functionally conserved from yeast to humans...
  12. pmc Tid1/Rdh54 promotes dissociation of Dmc1 from nonrecombinogenic sites on meiotic chromatin
    Teresa M Holzen
    Department of Radiation and Cellular Oncology, University of Chicago, Illinois 60637, USA
    Genes Dev 20:2593-604. 2006
    ..The results raise the possibility that ATP hydrolysis-dependent disruption of nonproductive recombinase-DNA interactions is a feature shared with other homologous recombination systems...
  13. ncbi The functional response of upstream DNA to dynamic supercoiling in vivo
    Fedor Kouzine
    Laboratory of Pathology, National Cancer Institute, 10 Center Drive, Building 10, Room 2N106, Bethesda, Maryland 20892 1500, USA
    Nat Struct Mol Biol 15:146-54. 2008
    ..These results indicate that mechanical stresses, constrained by architectural features of DNA and chromatin, may broadly contribute to gene regulation...
  14. ncbi ChIP-on-chip analysis of DNA topoisomerases
    Rodrigo Bermejo
    Fondazione Italiana per la Ricerca sul Cancro, Institute of Molecular Oncology Foundation, Milan, Italy
    Methods Mol Biol 582:103-18. 2009
    ..By using this approach, novel aspects of DNA topoisomerase function in chromosome metabolism might be unmasked...
  15. ncbi DNA topoisomerases in cancer chemotherapy: using enzymes to generate selective DNA damage
    John L Nitiss
    Molecular Pharmacology Department, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    Curr Opin Investig Drugs 3:1512-6. 2002
    ..These investigations into the mechanisms of action of topoisomerase-targeting agents should aid in the design of dinical protocols that optimize the activity of these agents...
  16. pmc DNA Topoisomerases maintain promoters in a state competent for transcriptional activation in Saccharomyces cerevisiae
    Jakob Madsen Pedersen
    Laboratory of Genome Research, Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark
    PLoS Genet 8:e1003128. 2012
    To investigate the role of DNA topoisomerases in transcription, we have studied global gene expression in Saccharomyces cerevisiae cells deficient for topoisomerases I and II and performed single-gene analyses to support our findings...
  17. ncbi The 1.2-megabase genome sequence of Mimivirus
    Didier Raoult
    Unite des Rickettsies, Faculte de Medecine, CNRS UMR6020, Universite de la Mediterranee, 13385 Marseille Cedex 05, France
    Science 306:1344-50. 2004
    ..This new sequence data might help shed a new light on the origin of DNA viruses and their role in the early evolution of eukaryotes...
  18. ncbi Structure, molecular mechanisms, and evolutionary relationships in DNA topoisomerases
    Kevin D Corbett
    Department of Molecular and Cellular Biology, University of California, Berkeley, California 94720, USA
    Annu Rev Biophys Biomol Struct 33:95-118. 2004
    ..A synthesis of these approaches has provided researchers with new physical insights into how topoisomerases employ chemistry and allostery to direct the large-scale molecular motions needed to pass DNA strands through each other...
  19. ncbi Topoisomerase function during bacterial responses to environmental challenge
    Shan Rui
    Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA
    Front Biosci 8:d256-63. 2003
    ....
  20. pmc Mutations in recombinational repair and in checkpoint control genes suppress the lethal combination of srs2Delta with other DNA repair genes in Saccharomyces cerevisiae
    H L Klein
    Department of Biochemistry and Kaplan Cancer Center, New York University School of Medicine, 550 First Ave, New York, NY 10016, USA
    Genetics 157:557-65. 2001
    ..However, cells do not achieve wild-type growth rates, suggesting that unrepaired damage is still present and may lead to chromosome loss...
  21. ncbi Single molecule imaging of Tid1/Rdh54, a Rad54 homolog that translocates on duplex DNA and can disrupt joint molecules
    Amitabh V Nimonkar
    Section of Microbiology, University of California, Davis, California 95616, USA
    J Biol Chem 282:30776-84. 2007
    ..The ability of Tid1 translocation to clear DNA of proteins and to migrate recombination intermediates may be of critical importance for DNA repair and chromosome dynamics...
  22. ncbi Arabidopsis SPO11-2 functions with SPO11-1 in meiotic recombination
    Nicola J Stacey
    Department of Cell and Developmental Biology, John Innes Centre, Colney, Norwich, NR4 7UH, UK
    Plant J 48:206-16. 2006
    ..Thus, the three Arabidopsis Spo11 homologues appear to function in two discrete processes, i.e. AtSPO11-1 and AtSPO11-2 in meiotic recombination and AtSPO11-3 in DNA replication...
  23. ncbi Roles of DNA topoisomerases in chromosome segregation and mitosis
    Felipe Cortés
    Department of Cell Biology, Faculty of Biology, University of Seville, Avda Reina Mercedes 6, E 41012 Seville, Spain
    Mutat Res 543:59-66. 2003
    b>DNA topoisomerases are highly specialized nuclear enzymes that perform topological changes in the DNA molecule in a very precise and unique fashion...
  24. ncbi (-)-Menthol inhibits DNA topoisomerases I, II alpha and beta and promotes NF-kappaB expression in human gastric cancer SNU-5 cells
    Jing Pin Lin
    School of Chinese Medicine and Department of Microbiology, China Medical University, Taichung City, 400, Taiwan
    Anticancer Res 25:2069-74. 2005
    ..These data suggest that (-)-Menthol may induce cytotoxicity through inhibiting gene expression of topoisomerase I, IIalpha and IIbeta and promoting the gene expression of NF-kappaB in SNU-5 cells...
  25. ncbi Yeast recombination factor Rdh54 functionally interacts with the Rad51 recombinase and catalyzes Rad51 removal from DNA
    Peter Chi
    Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    J Biol Chem 281:26268-79. 2006
    ..Rad51 complex formation. The Rdh54 expression and purification procedures described here should facilitate the functional dissection of this DNA recombination/repair factor...
  26. ncbi A DNA-binding surface of SPO11-1, an Arabidopsis SPO11 orthologue required for normal meiosis
    Yoshinori Shingu
    Cellular and Molecular Biology Laboratory, RIKEN Advanced Science Institute, Wako Shi, Saitama, Japan
    FEBS J 277:2360-74. 2010
    ..Thus, the Gly215, Arg222 and Arg223 residues of SPO11-1 form a DNA-binding surface that is functional in meiosis...
  27. pmc A DNA-translocating Snf2 molecular motor: Saccharomyces cerevisiae Rdh54 displays processive translocation and extrudes DNA loops
    Tekkatte Krishnamurthy Prasad
    Department of Biochemistry and Molecular Biophysics, Columbia University, 650 West 168th Street, New York, NY 10032, USA
    J Mol Biol 369:940-53. 2007
    ..Our work, together with other recent studies, suggests that translocation-coupled DNA loop extrusion is a common mechanistic feature among the Snf2-family of chromatin-remodeling proteins...
  28. ncbi Reverse gyrase: an insight into the role of DNA-topoisomerases
    Marc Nadal
    Equipe Virologie Moléculaire et Microbiologie, Laboratoire de Génétique et de Biologie Cellulaire, CNRS UMR 8159, Universite de Versailles St Quentin en Yvelines, Batiment Buffon, 78 035 Versailles, France
    Biochimie 89:447-55. 2007
    ..These data give us a new insight in the cellular role of reverse gyrase. Moreover, it has been proposed that reverse gyrase has been implicated in genome stability...
  29. ncbi Molecular characterization of homologues of both subunits A (SPO11) and B of the archaebacterial topoisomerase 6 in plants
    F Hartung
    Institute of Plant Genetics and Crop Plant Research IPK, Corrensstrasse 3, D 06466 Gatersleben, Germany
    Gene 271:81-6. 2001
    ..Our data suggest that plants possess in contrast to other eukaryotes an additional archaebacterial kind of topoisomerase...
  30. ncbi DNA topoisomerases as anticancer drug targets: from the laboratory to the clinic
    J A Holden
    Department of Pathology, University of Utah, Salt Lake City 84132, USA
    Curr Med Chem Anticancer Agents 1:1-25. 2001
    b>DNA topoisomerases play important roles in basic cellular biology. Recently they have been identified as the molecular targets of a variety of pharmaceutical agents. Some of the drugs that target the topoisomerases are anticancer drugs...
  31. ncbi DNA topoisomerases as targets for antiprotozoal therapy
    R P Bakshi
    Department of Medicine, The Johns Hopkins University, Baltimore, MD 21205, USA
    Mini Rev Med Chem 3:597-608. 2003
    ..b>DNA topoisomerases are clinically relevant targets for anti-cancer and anti-bacterial agents...
  32. ncbi DNA topoisomerases of Leishmania: the potential targets for anti-leishmanial therapy
    Benu Brata Das
    Department of Molecular Parasitology, Indian Institute of Chemical Biology Kolkata, India
    Adv Exp Med Biol 625:103-15. 2008
    ..This ancient eukaryote shows variable genetic diversity in their life cycle, wherein DNA topoisomerases play a key role in cellular processes affecting the topology and organization ofintracellular DNA...
  33. pmc Promotion of Rad51-dependent D-loop formation by yeast recombination factor Rdh54/Tid1
    G Petukhova
    Department of Molecular Medicine and Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78245 3207, USA
    Genes Dev 14:2206-15. 2000
    ..Efficient D-loop formation occurs with even topologically relaxed DNA, suggesting that via specific protein-protein interactions, the negative supercoils produced by Rdh54 are used by Rad51 for making DNA joints...
  34. pmc Genetic requirements for RAD51- and RAD54-independent break-induced replication repair of a chromosomal double-strand break
    L Signon
    Department of Biology and Rosenstiel Center, Brandeis University, Waltham, Massachusetts 02254 9110, USA
    Mol Cell Biol 21:2048-56. 2001
    ..The similar genetic requirements for BIR and telomere maintenance in the absence of telomerase also suggest that these two processes proceed by similar mechanisms...
  35. ncbi Enzymes that cleave and religate DNA at high temperature: the same story with different actors
    Marie Claude Serre
    Laboratoire d Enzymologie des Acides Nucleiques, Institut de Genetique et Microbiologie, Universite Paris Sud, 91405 Orsay Cedex, France
    Prog Nucleic Acid Res Mol Biol 74:37-81. 2003
  36. ncbi Molecular design of cholesterols as inhibitors of DNA polymerase alpha
    Masahiko Oshige
    Frontier Research Center for Genome and Drug Discovery, Department of Applied Biological Science, Faculty of Science and Technology, and Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda shi, Chiba ken 278 8510, Japan
    J Med Chem 47:4971-4. 2004
    ..alpha activity. With pol.alpha, these compounds acted by competing with the template-primer DNA and noncompetitively with the substrate...
  37. pmc Unique biological properties and molecular mechanism of 5,6-bridged quinolones
    David R Macinga
    Procter and Gamble Pharmaceuticals, Mason, Ohio 45040, USA
    Antimicrob Agents Chemother 47:2526-37. 2003
    ..These results demonstrate that the 5,6-bridged quinolones act via a mechanism that is related to but qualitatively different from that of typical quinolones...
  38. ncbi Design, docking, and synthesis of novel indeno[1,2-c]isoquinolines for the development of antitumor agents as topoisomerase I inhibitors
    Won Jea Cho
    College of Pharmacy and Research Institute of Drug Development, Chonnam National University, Kwangju 500 757, Republic of Korea
    Bioorg Med Chem Lett 17:3531-4. 2007
    ..The synthesized compounds were tested in vitro for cytotoxicity and DNA-topoisomerase 1 (top 1) inhibitory activity. The dramatic enhancement of top 1 inhibitory activity of 4 was explained by a docking study using the FlexX program...
  39. ncbi Combined inhibition of topoisomerases: a phase I. Study of irinotecan and epirubicin
    Jimmy J Hwang
    Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC, USA
    Oncology (Williston Park) 17:46-51. 2003
    ..Other toxicities were acceptable and non-dose-limiting. Accrual of patients continues, at level 3A (irinotecan at 75 mg/m2, epirubicin at 25 mg/m2)...
  40. pmc Genomic transcriptional response to loss of chromosomal supercoiling in Escherichia coli
    Brian J Peter
    Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720 3204, USA
    Genome Biol 5:R87. 2004
    ..In turn, supercoiling influences local DNA structure and can affect gene expression. We used microarrays representing nearly the entire genome of Escherichia coli MG1655 to examine the dynamics of chromosome structure...
  41. ncbi Apoptosis induced by topoisomerase inhibitors
    Olivier Sordet
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892 4255, USA
    Curr Med Chem Anticancer Agents 3:271-90. 2003
    ..Finally, we will review the recent observations that support a role for topoisomerases in chromatin fragmentation during the execution phase of apoptosis...
  42. ncbi Synthesis and biological assays of E-ring analogs of camptothecin and homocamptothecin
    Raghuram S Tangirala
    Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA
    Bioorg Med Chem 14:6202-12. 2006
    ..The results provide insights into the structural features of the camptothecin E-ring that affect biological activity...
  43. pmc Endonuclease cleavage of blocked replication forks: An indirect pathway of DNA damage from antitumor drug-topoisomerase complexes
    George Hong
    Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA
    Proc Natl Acad Sci U S A 100:5046-51. 2003
    ..These results suggest that an indirect pathway of branched-DNA cleavage contributes to the cytotoxicity of antitumor drugs that target DNA topoisomerases.
  44. ncbi The mitotic spindle checkpoint is a critical determinant for topoisomerase-based chemotherapy
    Celia Vogel
    Institute for Molecular Biology and Tumor Research IMT, Philipps University Marburg, D 35037 Marburg, Germany
    J Biol Chem 280:4025-8. 2005
    ..Its frequent inactivation in human cancer might contribute to the observed resistance of tumor cells to these chemotherapeutic drugs...
  45. ncbi Tracking topoisomerase activity at the single-molecule level
    G Charvin
    LPS, ENS, UMR 8550 CNRS, 75231 Paris Cedex 05, France
    Annu Rev Biophys Biomol Struct 34:201-19. 2005
    ..These results shed new light on the mechanism of these enzymes and their function in vivo...
  46. ncbi Inhibitors of topoisomerases as anticancer drugs: problems and prospects
    B S Dwarakanath
    Institute of Nuclear Medicine and Allied Sciences, Brig S K Mazumdar Marg, Delhi 110054, India
    Indian J Exp Biol 42:649-59. 2004
    b>DNA topoisomerases, which solve topological problems associated with various DNA transactions, are the targets of many therapeutic agents...
  47. pmc Elongation by RNA polymerase II on chromatin templates requires topoisomerase activity
    Neelima Mondal
    Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Nucleic Acids Res 31:5016-24. 2003
    ....
  48. ncbi Nanoparticle drug delivery system for intravenous delivery of topoisomerase inhibitors
    Joshua Williams
    ImaRx Therapeutics, Inc, 1635 E 18th St, Tucson, AZ 85719, USA
    J Control Release 91:167-72. 2003
    ..In vivo studies in nude mice showed prolonged half-life of the active (lactone form) drug in whole blood and increased efficacy compared to Camptosar in a mouse xenograft tumor model...
  49. pmc Glutathione depletion induced by c-Myc downregulation triggers apoptosis on treatment with alkylating agents
    Annamaria Biroccio
    Experimental Chemotherapy Laboratory, Experimental Research Center, Regina Elena Cancer Institute, Rome 00158, Italy
    Neoplasia 6:195-206. 2004
    ..All together, these results demonstrate that GSH plays a key role in governing c-Myc-dependent drug-induced apoptosis...
  50. ncbi Design, synthesis and structure-activity relationship studies of novel indazole analogues as DNA gyrase inhibitors with Gram-positive antibacterial activity
    Akihiko Tanitame
    Chemistry Research Laboratories, Dainippon Pharmaceutical Co, Ltd, 33 94, Enoki, Suita, Osaka 564 0053, Japan
    Bioorg Med Chem Lett 14:2857-62. 2004
    ....
  51. ncbi Topoisomerase inhibitor camptothecin sensitizes mouse hepatocytes in vitro and in vivo to TNF-mediated apoptosis
    Hannes Hentze
    Biochemical Pharmacology, University of Konstanz, Konstanz, Germany
    Hepatology 39:1311-20. 2004
    ....
  52. ncbi [Screening of DNA topoisomerase inhibitors]
    Toshiwo Andoh
    Department of Bioinformatics, Faculty of Engineering, Soka University, 1 236 Tangi cho, Hachioji, Tokyo 192 8577, Japan
    Gan To Kagaku Ryoho 31:495-500. 2004
    ..doxorubicin: DOX) and irinotecan (CPT-11), efficacious antitumor drugs widely used in clinics, target DNA topoisomerases (topo) in vivo...
  53. ncbi 6-Arylamino-7-chloro-quinazoline-5,8-diones as novel cytotoxic and DNA topoisomerase inhibitory agents
    Hyen Joo Park
    College of Pharmacy, Ewha Womans University, 11 1 Daehyun Dong, Seodaemun Ku, Seoul 120 750, South Korea
    Bioorg Med Chem Lett 14:3385-8. 2004
    ..To further investigate the cytotoxic mechanism, the effects of test compounds on DNA topoisomerase I and II activities have been assessed...
  54. ncbi Inhibitory effects of cholesterol derivatives on DNA polymerase and topoisomerase activities, and human cancer cell growth
    Chisato Ishimaru
    Laboratory of Food and Nutritional Sciences, Department of Nutritional Science, Kobe Gakuin University, Kobe, Hyogo 651 2180, Japan
    Lipids 43:373-82. 2008
    ..These results suggested that the effect of cell cycle arrest might be effective on both pols and topos activities. From these findings, the action mode of cholesterol derivatives as anti-cancer compounds is discussed...
  55. ncbi Coupling DNA supercoiling to transcription in defined protein systems
    Fenfei Leng
    Department of Chemistry and Biochemistry, Florida International University, Miami, Florida 33199, USA
    J Biol Chem 279:47564-71. 2004
    ..Under optimal conditions, the twin domain pathway of TCDS rapidly and efficiently generated superhelicity levels more than twice that typically found in vivo...
  56. ncbi Rad9 protects cells from topoisomerase poison-induced cell death
    David Loegering
    Division of Oncology Research, Mayo Clinic, Rochester, Minnesota 55905, USA
    J Biol Chem 279:18641-7. 2004
    ..Collectively, these results suggest that the predominant role of Rad9 in ES cells is to promote survival after replicative stress and topoisomerase-mediated DNA damage...
  57. ncbi First evidence for helical transitions in supercoiled DNA by amyloid Beta Peptide (1-42) and aluminum: a new insight in understanding Alzheimer's disease
    Muralidhar L Hegde
    Department of Biochemistry and Nutrition, Central Food Technological Research Institute, Mysore 570013, India
    J Mol Neurosci 22:19-31. 2004
    ..A new hypothetical model explaining the potential toxicity of Abeta and Al in terms of their DNA binding properties leading to DNA conformational alteration is proposed...
  58. ncbi Cytotoxicity and DNA topoisomerase inhibitory activity of benz[f]indole-4,9-dione analogs
    Hyen Joo Park
    College of Pharmacy, Ewha Womans University, Seoul, Korea
    Biosci Biotechnol Biochem 67:1944-9. 2003
    ..A549 (lung cancer), Col2 (colon cancer), and SNU-638 (stomach cancer), and also for the inhibition of human DNA topoisomerases I and II activity in vitro...
  59. ncbi Antitumor triptycene bisquinones: a novel synthetic class of dual inhibitors of DNA topoisomerase I and II activities
    Buna Wang
    Anti Cancer Drug Laboratory, Division of Biology, Ackert Hall, Kansas State University, Manhattan 66506 4901, USA
    Anticancer Drugs 14:503-14. 2003
    ..Because of their ability to target nucleoside transport and topoisomerase activities, synthetic TT bisquinones might represent a novel class of bifunctional drugs valuable to develop new means of polychemotherapy and circumvent MDR...
  60. ncbi Highly cytotoxic benzo[c]pyrido[2,3,4-kl]acridines
    Sarah Chackal
    Institut de Chimie Pharmaceutique Albert Lespagnol, EA 2692, Universite de Lille 2, BP 83, 59006 Lille, France
    Bioorg Med Chem Lett 13:943-6. 2003
    ..on the A and E rings were synthesized and evaluated for their capacity to bind to DNA and to inhibit DNA topoisomerases. Potent cytotoxic compounds were discovered but no strict correlation with their DNA binding affinity and ..
  61. ncbi DNA manipulators: caught in the act
    Anita Changela
    Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, 2153 Sheridan Road, Evanston, IL 60208 3500, USA
    Curr Opin Struct Biol 13:15-22. 2003
    ..in promoting DNA rearrangements, including site-specific recombinases, DNA helicases, transposases and DNA topoisomerases. Recent structures of protein-DNA reaction intermediates trapped in various states of DNA remodeling, ..
  62. ncbi Structural analysis of isosteviol and related compounds as DNA polymerase and DNA topoisomerase inhibitors
    Yoshiyuki Mizushina
    Laboratory of Food and Nutritional Sciences, Department of Nutritional Science, Kobe Gakuin University, Nishi ku, Kobe, Hyogo 651 2180, Japan
    Life Sci 77:2127-40. 2005
    ..0%). The relationship between the structure of stevioside-based compounds and these activities were discussed...
  63. ncbi Molecular and pharmacological strategies to overcome multidrug resistance
    J A Shabbits
    Department of Advanced Therapeutics, BC Cancer Agency, Vancouver, BC, V5Z 4E6, Canada
    Expert Rev Anticancer Ther 1:585-94. 2001
    ..We also describe how liposomal drug delivery systems can be utilized to aid in achieving these goals...
  64. pmc DNA bending, compaction and negative supercoiling by the architectural protein Sso7d of Sulfolobus solfataricus
    Alessandra Napoli
    Institute of Protein Biochemistry and Enzymology, Consiglio Nazionale delle Ricerche, Via Pietro Castellino 111, 80131 Naples, Italy
    Nucleic Acids Res 30:2656-62. 2002
    ..The proposed biological relevance of these observations is that these proteins might model the behaviour of DNA in constrained chromatin environments...
  65. ncbi [Interpretive reading of the antibiogram of enterobacteria]
    Ferran Navarro Risueño
    Servicio de Microbiologia, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma de Barcelona, Spain
    Enferm Infecc Microbiol Clin 20:225-34. 2002
    ..Resistance to quinolones is due to point and sequence mutations which may be selected by initially active fluoroquinolones and cause a stepwise increase of resistance...
  66. pmc Effect of non-steroidal anti-inflammatory drugs on colon carcinoma Caco-2 cell responsiveness to topoisomerase inhibitor drugs
    P Ricchi
    Dipartimento di Biologia e Patologia Cellulare e Molecolare L Califano, Istituto di Endocrinologia ed Oncologia Sperimentale G Salvatore del Consiglio Nazionale delle Ricerche, , Via S Pansini 5, 80131 Naples, Italy
    Br J Cancer 86:1501-9. 2002
    ..This provides a plausible mechanism for the inhibition of apoptosis and increase in survival observed in anticancer drug and aspirin co-treatment...
  67. pmc Inferring global topology from local juxtaposition geometry: interlinking polymer rings and ramifications for topoisomerase action
    Zhirong Liu
    Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada
    Biophys J 90:2344-55. 2006
    ..statistical mechanical principles emerging from these findings suggest that it is physically possible for DNA topoisomerases to decatenate effectively by acting selectively on juxtapositions with specific "hooked" geometries...
  68. ncbi Selective inhibition of the activities of both eukaryotic DNA polymerases and DNA topoisomerases by elenic acid
    Yoshiyuki Mizushina
    Laboratory of Food and Nutritional Sciences, Department of Nutritional Science, Kobe Gakuin University, Nishi ku Kobe, Hyogo, Japan
    Biochem Pharmacol 63:399-407. 2002
    ..Interestingly, EA was also an inhibitor of DNA topoisomerases I and II, although the enzymatic characteristics including modes of action, amino acid sequences and three-..
  69. ncbi Kinetic studies of the binding of acridinecarboxamide topoisomerase poisons to DNA: implications for mode of binding of ligands with uncharged chromophores
    Laurence P G Wakelin
    School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia
    J Med Chem 45:894-901. 2002
    ..This difference may have relevance to the ability of DACA to be a dual poison of both topoisomerases I and II...
  70. ncbi An MCL1-overexpressing Burkitt lymphoma subline exhibits enhanced survival on exposure to serum deprivation, topoisomerase inhibitors, or staurosporine but remains sensitive to 1-beta-D-arabinofuranosylcytosine
    Julie A Vrana
    Department of Pharmacology, Dartmouth Medical School, Hanover, New Hampshire 03755 3835, USA
    Cancer Res 62:892-900. 2002
    ....
  71. ncbi [Myelotoxity of the nuclear enzyme inhibitors irinotecan and etoposide]
    G V Karpova
    Eksp Klin Farmakol 69:42-7. 2006
    ..On longer terms (from three to six months) after irinotecan and etoposide injection, there were a moderate decrease in the red blood cells and hematocrit, an increase of the MCV and MCHC indices, and premature thymus involution...
  72. ncbi DNA topoisomerases in cancer chemotherapy: basic and applied aspects
    F Cortes
    Department of Cellular Biology, Faculty of Biology, University of Seville, Spain
    Cytobios 106:217-27. 2001
    ..In this context the DNA topoisomerases have been generally considered as good candidates to play a role in the enzymatic repair processes going on ..
  73. ncbi Influence of G2 arrest on the cytotoxicity of DNA topoisomerase inhibitors toward human carcinoma cells with different p53 status
    Przemyslaw Bozko
    Department of Pharmaceutical Technology and Biochemistry, Technical University of Gdansk, Poland
    Acta Biochim Pol 49:109-19. 2002
    ..These results strongly suggest that even prolonged cell cycle arrest in the G2 phase of the cell cycle is not necessarily coupled to efficient DNA repair and enhanced cellular survival as generally believed...
  74. ncbi Catalytic transformations of supercoiled DNA as studied by flow linear dichroism technique
    Alexander Gabibov
    Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia
    FEBS J 272:6336-43. 2005
    ..Moreover, FLD assay can be applied to any enzymatic reaction that involves scDNA as a substrate. It also provides a new way of screening drugs dynamically and is likely to be potent in various biomedical applications...
  75. ncbi Embryonic stem cells deficient for Brca2 or Blm exhibit divergent genotoxic profiles that support opposing activities during homologous recombination
    Teresa Marple
    The Department of Molecular Medicine and Institute of Biotechnology, The University of Texas Health Science Center at San Antonio, 15355 Lambda Drive San Antonio, TX 78245 3207, USA
    Mutat Res 602:110-20. 2006
    ..These divergent profiles support the notion that Brca2 and Blm perform opposing functions during HR in mouse ES cells...
  76. ncbi Role of topoisomerases in cytotoxicity induced by DNA ligand Hoechst-33342 and UV-C in a glioma cell line
    Shailja Singh
    Division of Biocybernetics, Institute of Nuclear Medicine and Allied Sciences, Delhi, India
    Indian J Exp Biol 43:313-23. 2005
    ..Cytotoxicity of Hoechst-33342 arises due to its interference in the breakage-rejoining reaction of DNA topoisomerases by stabilization of cleavable complexes...
  77. ncbi The epidermal growth factor receptor and human topoisomerases represent potential cellular targets of oligomeric procyanidins
    Diana Fridrich
    Institute of Applied Biosciences, Section of Food Toxicology, University of Karlsruhe TH, Kaiserstrasse 12, Karlsruhe, Germany
    Mol Nutr Food Res 51:192-200. 2007
    ....
  78. ncbi Design, synthesis and biological evaluation of new oligopyrrole carboxamides linked with tricyclic DNA-intercalators as potential DNA ligands or topoisomerase inhibitors
    Marie Hélène David-Cordonnier
    INSERM U837 JPARC, Equipe N degrees 4, Institut de Recherches sur le Cancer de Lille, Place de Verdun, 59045 Lille Cedex, France
    Eur J Med Chem 42:752-71. 2007
    ....
  79. ncbi Synthesis, DNA binding, topoisomerase inhibition and cytotoxic properties of 2-chloroethylnitrosourea derivatives of hoechst 33258
    Krzysztof Bielawski
    Department of Medicinal Chemistry and Drug Technology, Medical University of Białystok, Poland
    Biol Pharm Bull 28:1004-9. 2005
    ..Mechanistic studies revealed that these compounds act as topoisomerase I (topo I) or topoisomerase II (topo II) inhibitors in plasmid relaxation assays...
  80. ncbi Inhibitory effect of conjugated eicosapentaenoic acid on mammalian DNA polymerase and topoisomerase activities and human cancer cell proliferation
    Yuko Yonezawa
    Laboratory of Food and Nutritional Sciences, Department of Nutritional Science, Kobe Gakuin University, Nishi ku, Kobe, Hyogo 651 2180, Japan
    Biochem Pharmacol 70:453-60. 2005
    ..acid (cEPA) selectively inhibited the activities of mammalian DNA polymerases (pols) and human DNA topoisomerases (topos) [Yonezawa Y, Tsuzuki T, Eitsuka T, Miyazawa T, Hada T, Uryu K, et al...
  81. ncbi Adeno-associated virus mediated endostatin gene therapy in combination with topoisomerase inhibitor effectively controls liver tumor in mouse model
    Sung Yi Hong
    Department of Surgery, Yonsei University College of Medicine, Youngdong PO Box 1217, Seoul, Korea
    World J Gastroenterol 10:1191-7. 2004
    ..However, a sustained and high protein delivery is required to achieve the desired therapeutic effects. We evaluated the impact of topoisomerase inhibitors in rAAV delivered endostatin gene therapy in a liver tumor model...
  82. ncbi Cellular profiling of small-molecule bioactivities: an alternative tool for chemical biology
    Thorsten Berg
    Department of Molecular Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany
    Angew Chem Int Ed Engl 44:5008-11. 2005
  83. ncbi The molecular perspective: DNA topoisomerases
    David S Goodsell
    The Scripps Research Institute, Department of Molecular Biology, La Jolla, California 92037, USA
    Stem Cells 20:470-1. 2002
  84. ncbi DNA gyrase and topoisomerase IV mutations in an in vitro fluoroquinolone-resistant Coxiella burnetii strain
    Iosif Vranakis
    Laboratory of Clinical Bacteriology, Parasitology, Zoonoses, and Geographical Medicine WHO Collaborating Center, Medical School, University of Crete, Heraklion, Greece
    Microb Drug Resist 16:111-7. 2010
    ..The present study adds additional potential mutations in the DNA topoisomerases that may be involved in fluoroquinolone resistance in C...
  85. pmc Genome of crocodilepox virus
    C L Afonso
    Plum Island Animal Disease Center, United States Department of Agriculture, Greenport, New York, NY 11944, USA
    J Virol 80:4978-91. 2006
    ..genomic region, including 7 genes encoding GyrB-like ATPase domains similar to those in cellular type IIA DNA topoisomerases, suggestive of novel ATP-dependent functions...
  86. ncbi Delphinidin modulates the DNA-damaging properties of topoisomerase II poisons
    Melanie Esselen
    Section of Food Toxicology, Institute of Applied Biosciences, Universitat Karlsruhe TH, Adenauerring 20A, 76131 Karlsruhe, Germany
    Chem Res Toxicol 22:554-64. 2009
    ..O., Larsen, M. K., Boege, F., and Marko, D. (2005) Anthocyanidins modulate the activity of human DNA topoisomerases I and II and affect cellular DNA integrity. Chem. Res. Toxicol. 18, 1395-404]...
  87. ncbi Transcriptional responses of Bacillus subtillis and thuringiensis to antibiotics and anti-tumour drugs
    Mouldy Sioud
    Department of Immunology, The Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, N 0310 Oslo, Norway
    Int J Mol Med 23:33-9. 2009
    ..This process is regulated by type I and type II DNA topoisomerases that are targets for microbial antibiotics and/or anti-tumour drugs...
  88. ncbi Beta-carboline alkaloids bind DNA
    Shohreh Nafisi
    Department of Chemistry, Azad University, Central Tehran Branch IAUCTB, Tehran, Iran
    J Photochem Photobiol B 100:84-91. 2010
    ..The mechanistic studies indicate that beta-carboline derivatives inhibit DNA topoisomerases and interfere with DNA synthesis...
  89. pmc Characterization of the reverse gyrase from the hyperthermophilic archaeon Pyrococcus furiosus
    K M Borges
    Center of Marine Biotechnology, University of Maryland Biotechnology Institute, Baltimore, USA
    J Bacteriol 179:1721-6. 1997
    ..indicates that all known reverse gyrase topoisomerase modules form a subgroup inside subfamily IA of type I DNA topoisomerases (sensu Wang [J. C. Wang, Annu. Rev. Biochem. 65:635-692, 1996])...
  90. ncbi Pharmacological basis for cladribine resistance in a human acute T lymphoblastic leukaemia cell line selected for resistance to etoposide
    K Lotfi
    Department of Medicine and Care, Clinical Pharmacology, Faculty of Health Sciences, Linkoping, Sweden
    Br J Haematol 113:339-46. 2001
    ..Furthermore, these results indicate that there is a common factor in the regulation of nucleotide-degrading enzymes and DNA topoisomerases, which may be altered in cross-resistant cells.
  91. ncbi Partial purification and characterization of Trichomonas vaginalis DNA topoisomerase II
    Somphong Sithiprom
    Department of Protozoology, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
    Southeast Asian J Trop Med Public Health 40:877-85. 2009
    b>DNA topoisomerases regulate conformational changes in DNA topology by catalyzing the breakage and rejoining of DNA strands during the cell cycle...
  92. ncbi Prolonged survival in a patient with BRCA2 associated metastatic pancreatic cancer after exposure to camptothecin: a case report and review of literature
    Edward James
    Department of Internal Medicine, Hospital of St Raphael, New Haven, Connecticut, USA
    Anticancer Drugs 20:634-8. 2009
    ..b>DNA topoisomerases are nuclear enzymes responsible for the regulation of DNA topology...
  93. pmc Cell cycle-coupled relocation of types I and II topoisomerases and modulation of catalytic enzyme activities
    K N Meyer
    Medizinische Poliklinik, University of Wurzburg, Germany
    J Cell Biol 136:775-88. 1997
    We visualized DNA topoisomerases in A431 cells and isolated chromosomes by isoenzyme-selective immunofluorescence microscopy. In interphase, topoisomerase I mainly had a homogeneous nuclear distribution...
  94. ncbi Recent advances in the development of dual topoisomerase I and II inhibitors as anticancer drugs
    S Salerno
    Dipartimento di Scienze Farmaceutiche, Universita di Pisa, Via Bonanno 6, I 56126 Pisa, Italy
    Curr Med Chem 17:4270-90. 2010
    b>DNA topoisomerases (topos) are essential enzymes that regulate the topological state of DNA during cellular processes such as replication, transcription, recombination, and chromatin remodeling...
  95. ncbi Formaldehyde-induced alkylation of a 2'-aminoglucose rebeccamycin derivative to both A.T and G.C base pairs in DNA
    C Bailly
    INSERM U 524 et Laboratoire de Pharmacologie Antitumorale du Centre Oscar Lambret, 59045 Lille, France
    J Med Chem 43:4711-20. 2000
    ..Their anticancer activities are associated with their capacities to interact with DNA and to inhibit DNA topoisomerases. Previous studies revealed that the planar indolocarbazole chromophore can intercalate into DNA, locating ..
  96. ncbi Molecular modelling studies on the interactions of human DNA topoisomerase IB with pyridoxal-compounds
    Serge Christmann-Franck
    Département de Biologie et Pharmacologie Structurales, CNRS UMR 8113, Institut Gustave Roussy et ENS Cachan, 61 Avenue du President Wilson, 94235 Cachan Cedex, France
    Biochimie 89:468-73. 2007
    Candida guilliermondii and human DNA topoisomerases I are inhibited by PL (pyridoxal), PLP (pyridoxal 5'-phosphate) and PLP-AMP (pyridoxal 5'-diphospho-5'-adenosine) (PL<PLP<PLP-AMP)...
  97. pmc Dynamics of human DNA topoisomerases IIalpha and IIbeta in living cells
    Morten O Christensen
    Department of Clinical Chemistry, Medizinische Poliklinik, University of Wurzburg, D 97070 Wurzburg, Germany
    J Cell Biol 157:31-44. 2002
    ..These observations suggest that topo II is not an immobile, structural component of the chromosomal scaffold or the interphase karyoskeleton, but rather a dynamic interaction partner of such structures...
  98. ncbi Use of yeast in the study of anticancer drugs targeting DNA topoisomerases: expression of a functional recombinant human DNA topoisomerase II alpha in yeast
    R A Wasserman
    Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, Massachusetts 02138
    Cancer Res 53:3591-6. 1993
    ..Overexpression of human DNA topoisomerase II alpha in yeast also provides a convenient source of the enzyme for in vitro studies...
  99. ncbi A gyrB-like gene from the hyperthermophilic bacterion Thermotoga maritima
    O Guipaud
    Institut de Genetique et Microbiologie, Universite Paris Sud, CNRS URA 1354, Orsay, France
    Gene 174:121-8. 1996
    ..It shares significant similarities with the ATPase subunits of mesophilic bacterial DNA topoisomerases II, either DNA gyrase (GyrB) or DNA topoisomerase IV (ParE)...
  100. ncbi Dissection of the nucleotide cycle of B. subtilis DNA gyrase and its modulation by DNA
    Thomas Göttler
    Division of Biophysical Chemistry, Biozentrum, University of Basel, CH 4056 Basel, Switzerland
    J Mol Biol 367:1392-404. 2007
    b>DNA topoisomerases catalyze the inter-conversion of different topological forms of DNA...
  101. ncbi Chemotherapy of leishmaniasis: past, present and future
    Jyotsna Mishra
    Head, Division of Clinical Microbiology, Department of Laboratory Medicine, All India Institute of Medical Sciences, New Delhi, India
    Curr Med Chem 14:1153-69. 2007
    ..440). However, the recent focus has been on identifying newer therapeutic targets in the parasite such as DNA topoisomerases. The present review describes the current understanding of different drugs against leishmaniasis, their ..

Research Grants45

  1. FUNCTION AND BIOLOGY OF EUKARYOTIC DNA TOPOISOMERASES
    Neil Osheroff; Fiscal Year: 2013
    ..Bacillus anthracis gyrase and topoisomerase IV will be used for some experiments to provide comparisons between the prokaryotic and eukaryotic type II enzymes. ..
  2. CONTROL OF DNA TOPOLOGY
    Yuk Ching Tse-Dinh; Fiscal Year: 2013
    ..The long term goals of this project are to understand how the activity, regulation and interactions of DNA topoisomerases control DNA topology and affect vital cellular functions...
  3. Topoisomerases: Target for Antitrypanosomal Therapy
    Theresa Shapiro; Fiscal Year: 2009
    ..Existing therapies are antique by contemporary standards and no vaccine is available. The DNA topoisomerases are enzymes essential for nucleic acid biosynthesis and cell survival and are proven targets for clinically ..
  4. ANTI-TOPOISOMERASE DRUG ACTION IN YEAST
    John L Nitiss; Fiscal Year: 2013
    ..An important model system for understanding the biological and biochemical properties of DNA topoisomerases is the yeast Saccharomyces cerevisiae...
  5. Structural studies of type I topoisomerases
    ALFONSO MONDRAGON; Fiscal Year: 2013
    ..PUBLIC HEALTH RELEVANCE: We propose to study the structure and mechanism of DNA topoisomerases, enzymes that are involved in several cellular processes, such as transcription, replication and ..
  6. DRUG SEQUENCING RESISTANCE IN MULTIPLE MYELOMA
    Daniel Sullivan; Fiscal Year: 1999
    ..is due to the concurrent expression of multiple mechanisms of resistance, perhaps including perturbations in DNA topoisomerases. The second major hypothesis of this application is that alterations in topoisomerase I and II (content, ..
  7. DICATIONIC DRUGS--METABOLISM AND TOXICITY
    Richard Tidwell; Fiscal Year: 1993
    ..II will focus on two previously described activities of dicationic agents, DNA binding and inhibition of DNA topoisomerases using a variety of biochemical techniques...
  8. DNA TOPOISOMERASES--BIOLOGICAL FUNCTIONS AND MECHANISMS
    James Wang; Fiscal Year: 1999
    ..of the mechanism of excision of rDNA rings from the chromosomal cluster when the total cellular level of DNA topoisomerases is low; the idea that the supercoiling of the DNA template by transcription is the underlying cause of ..
  9. HPV DNA REPLICATION: NOVEL HOST FACTORS
    Thomas Melendy; Fiscal Year: 2003
    The candidate, Thomas Melendy, earned his Ph.D. from UCLA in 1988, studying trypanosomal DNA topoisomerases with Dr. Dan S. Ray. While a postdoctoral fellow at Cold Spring Harbor Laboratory (1988-1994), he worked with Dr...
  10. Top3 Homologues in Lymphocyte Genome Stability and Aging
    ALBERT SHAW; Fiscal Year: 2009
    ..b>DNA topoisomerases carry out the sequential breakage and rejoining of DNA strands to resolve structures inherent in the ..
  11. FUNCTION AND MECHANISM OF DNA TOPOISOMERASE
    Tao Shih Hsieh; Fiscal Year: 2010
    ..b>DNA topoisomerases are the essential enzymes to facilitate these processes...
  12. Topoisomerases: Target for Antitrypanosomal Therapy
    Theresa Shapiro; Fiscal Year: 2006
    ..Existing therapies are antique by contemporary standards and no vaccine is available. The DNA topoisomerases are enzymes essential for nucleic acid biosynthesis and cell survival and are proven targets for clinically ..
  13. FUNCTIONAL AND MECHANISTIC STUDIES OF DNA TOPOISOMERASES
    Leroy Liu; Fiscal Year: 2001
    Our long-term objective is to understand the molecular mechanism and physiological function of multiple DNA topoisomerases. In the current application, we propose to study the roles of the two human topoisomerase II (TOP2) isoforms in ..
  14. FOURTH CONFERENCE ON DNA TOPOISOMERASES IN THERAPY
    Milan Potmesil; Fiscal Year: 1992
    We propose to organize the "Fourth Conference on DNA Topoisomerases in Therapy" at the NYUMC, in October 17-19, 1992...
  15. ENDONUCLEASE/TOPOISOMERASE NAEI
    MICHAEL TOPAL; Fiscal Year: 2002
    b>DNA topoisomerases, recombinases, endonucleases and ligases are basic to the genetic machinery of the cell. These enzymes are ubiquitous and essential for replication, transcription, recombination, and repair of DNA...
  16. MUTATIONAL ANALYSIS OF E COLI DNA TOPOISOMERASE III
    Russell DiGate; Fiscal Year: 2005
    DESCRIPTION (Provided by applicant): DNA topoisomerases are enzymes that alter the linking number of DNA and, as such, are responsible for topological inter- and intra-conversions within DNA molecules...
  17. INHIBITION OF DNA TOPOISOMERASES I AND II BY DMP840
    MARY DANKS; Fiscal Year: 1999
    ..Preliminary biochemical data indicate that DMP 840 is a novel compound in that it inhibits DNA topoisomerases I and II by a mechanisms different from inhibitors of topoisomerases now used clinically...
  18. TOPOISOMERASE TARGETED AGENTS--CHEMISTRY TO CHEMOTHERAPY
    David Graves; Fiscal Year: 2000
    b>DNA topoisomerases essential enzymes that modulate the topological state of DNA by making transient breaks in the genetic material...
  19. MECHANISM OF ENERGY COUPLING BY DNA TOPOISOMERASE II
    JANET LINDSLEY; Fiscal Year: 2002
    Type II DNA topoisomerases are essential enzymes that unlink intertwined chromosomes. By altering DNA topology they participate in chromosome segregation, condensation, replication, recombination and transcription...
  20. DNA TOPOISOMERASES--DNA INTERACTIONS AND AT CONTROL
    Frank Castora; Fiscal Year: 1990
    ..The specific goal of this proposal is to begin to elucidate the roles of DNA topoisomerases in the replication and metabolism of mtDNA...
  21. CELL KILLING BY TOPOISOMERASE ACTIVE ANTICANCER DRUGS
    James Wang; Fiscal Year: 2000
    The proposed project aims at the elucidation of molecular mechanisms of anticancer drugs targeting DNA topoisomerases and the physiological functions of mammalian DNA topoisomerases II beta, III alpha and III beta...
  22. DNA TOPOISOMERASES IN HEAT SHOCK GENE EXPRESSION
    Thomas Rowe; Fiscal Year: 1991
    Several drugs have recently been identified as specific inhibitors of eukaryotic DNA topoisomerases. We have shown that these inhibitors affect the regulation of eukaryotic heat shock gene expression suggesting a role for these enzymes in ..
  23. High Throughput Assay:Topoisomerase Enzyme Targets (RMI)
    JAMES STIVERS; Fiscal Year: 2005
    ..and utilize, in high throughput molecular screening applications, a novel continuous spectroscopic assay for DNA topoisomerases. These enzymes are established targets for anticancer, antibacterial and antiviral drug therapies, and this ..
  24. Vaults as New Targets for Modulating Tumor Response
    LEONARD ROME; Fiscal Year: 2003
    ..resistance protein, and breast cancer resistance protein, alterations in the essential nuclear enzymes, DNA topoisomerases, and induction of lung resistance-related protein (LRP), identified as the major vault protein (MVP)...
  25. DNA REPAIR AND ANTITOPOISOMERASE DRUG EFFECTS
    John L Nitiss; Fiscal Year: 2010
    ..in this proposal should enhance our understanding of the mechanisms of action of these drugs targeting DNA topoisomerases. A key question that this work will address is why drugs targeting different topoisomerases have different ..
  26. CONFORMATIONAL PROPERTIES OF DNA CATENANES
    Alexander V Vologodskii; Fiscal Year: 2010
    ..Combining computer simulations and experiments, we will try to understand the mechanism of high topological selectivity of DNA resolvases. ..
  27. DNA TOPOISOMERASES--BIOLOGICAL FUNCTIONS & MECHANISMS
    James Wang; Fiscal Year: 2003
    DESCRIPTION (from applicant's abstract): The DNA topoisomerases, a family of ubiquitous enzymes that participate in nearly all cellular processes involving DNA, catalyze the passage of DNA strands or double helices through one another...
  28. Development of a HTS system:topoisomerase targets (RMI)
    Yuk Ching Tse Dinh; Fiscal Year: 2004
    b>DNA topoisomerases are important targets for therapy against potential viral and bacterial pathogens...
  29. EUKARYOTIC TOPOISOMERASE I
    James J Champoux; Fiscal Year: 2010
    ....
  30. ANTITUMOR AGENTS AND THE BACTERIOPHAGE T4 TOPOISOMERASE
    Kenneth Kreuzer; Fiscal Year: 2001
    ..T4 provides a powerful model system for analyzing the mechanism of antitumor agents that inhibit type II DNA topoisomerases. T4 has been very well studied and is easy to manipulate with genetic, molecular and biochemical approaches...
  31. The Enzymology of M-MuLV and HIV Replication
    JAMES CHAMPOUX; Fiscal Year: 2009
    ..The analysis of reverse transcriptase fidelity during displacement synthesis will directly contribute to our understanding of how the virus rapidly evolves during progression to AIDS. ..
  32. HTS for agents that increase recognition of tumors by cytotoxic lymphocytes
    TIMOTHY HAGGERTY; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  33. Duke PREP: Minority Recruitment into Biomedical Sciences
    Kenneth Kreuzer; Fiscal Year: 2007
    ..The PREP scholars will be encouraged to take advantage of the full two-year experience, as long as they perform at an acceptable level and maintain an interest in pursuing a career in science. ..
  34. DNA GYRASE AND QUINOLONE RESISTANCE IN TUBERCULOSIS
    Karl Drlica; Fiscal Year: 2007
    ..abstract_text> ..
  35. Direct analysis of fork blockage and DNA repair in vivo
    Kenneth Kreuzer; Fiscal Year: 2003
    ..If the system is validated, many other kinds of DNA damage can presumably be analyzed in-future studies. ..
  36. DNA BINDING BY HUMAN TOPOISOMERASE I
    JAMES CHAMPOUX; Fiscal Year: 2003
    ..abstract_text> ..
  37. Tangle Analysis of DNA Recombinases & Related Proteins
    ISABEL DARCY; Fiscal Year: 2005
    ..Apart from the recombination systems investigated in this proposal, the tangle-analysis tools that we develop will be extended to other recombinases and used to investigate related systems such as topoisomerases. ..
  38. INITIATION OF DNA REPLICATION IN THE PHAGE T4 SYSTEM
    Kenneth Kreuzer; Fiscal Year: 2005
    ....
  39. Molecular Determinants of Mitochondrial Optic Atrophy
    SUSAN CLINE; Fiscal Year: 2005
    ..abstract_text> ..