type i dna topoisomerases

Summary

Summary: DNA TOPOISOMERASES that catalyze ATP-independent breakage of one of the two strands of DNA, passage of the unbroken strand through the break, and rejoining of the broken strand. DNA Topoisomerases, Type I enzymes reduce the topological stress in the DNA structure by relaxing the superhelical turns and knotted rings in the DNA helix.

Top Publications

  1. ncbi 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
  2. ncbi Topoisomerase I inhibitors: camptothecins and beyond
    Yves Pommier
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, 20892 4255, USA
    Nat Rev Cancer 6:789-802. 2006
  3. ncbi BLAP18/RMI2, a novel OB-fold-containing protein, is an essential component of the Bloom helicase-double Holliday junction dissolvasome
    Thiyam Ramsing Singh
    Division of Experimental Hematology and Cancer Biology, Cincinnati Children s Research Foundation, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA
    Genes Dev 22:2856-68. 2008
  4. ncbi Antitumour drugs impede DNA uncoiling by topoisomerase I
    Daniel A Koster
    Kavli Institute of Nanoscience, Faculty of Applied Sciences, Delft University of Technology, Lorentzweg 1, 2628 CJ Delft, The Netherlands
    Nature 448:213-7. 2007
  5. ncbi Srs2 and Sgs1-Top3 suppress crossovers during double-strand break repair in yeast
    Grzegorz Ira
    Rosenstiel Center and Department of Biology, Brandeis University, Waltham, MA 02454, USA
    Cell 115:401-11. 2003
  6. ncbi Hereditary ataxia SCAN1 cells are defective for the repair of transcription-dependent topoisomerase I cleavage complexes
    Ze Hong Miao
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    DNA Repair (Amst) 5:1489-94. 2006
  7. ncbi Mechanism of action of eukaryotic DNA topoisomerase I and drugs targeted to the enzyme
    Y Pommier
    Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, Bethesda, MD 20892 4255, USA
    Biochim Biophys Acta 1400:83-105. 1998
  8. ncbi Yeast Tdp1 and Rad1-Rad10 function as redundant pathways for repairing Top1 replicative damage
    John R Vance
    Plantaceutica, Incorporated, P O Box 12060, 99 Alexander Drive, Research Triangle Park, NC 27709 2060, USA
    Proc Natl Acad Sci U S A 99:13669-74. 2002
  9. ncbi Clinical applications of the camptothecins
    C H Takimoto
    Developmental Therapeutics Department, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Building 8, Room 5101, Bethesda Naval Hospital, Bethesda, MD 20892, USA
    Biochim Biophys Acta 1400:107-19. 1998
  10. 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

Research Grants

  1. Improving CPT-11 Efficacy Using Structural Biology
    MATTHEW REDINBO; Fiscal Year: 2007
  2. STRUCTURE/FUNCTION OF TWO DNA BINDING PROTEINS
    WILHELMUS HOL; Fiscal Year: 1999
  3. MECHANISM OF ACTION OF ANTITUMOR DRUGS
    Leroy F Liu; Fiscal Year: 2010
  4. Novel Direct Approaches Toward Bioactive Heterocycles
    Vladimir Gevorgyan; Fiscal Year: 2010
  5. SAR OF NOVEL TOPO I INHIBITOR AGAINST PROSTATE CANCER
    YUE WEI LEE; Fiscal Year: 2001
  6. ROLE OF TOPOISOMERASES IN DNA REPLICATION
    KENNETH MARIANS; Fiscal Year: 1990
  7. Anti-Cancer Drug Design Targeting Human Topoisomerase I
    Lance Stewart; Fiscal Year: 2002
  8. Novel Mechanisms by which RAD18 and POLZ affect Response to Anticancer Agents
    CHRISTINE ELIZABETH CANMAN; Fiscal Year: 2010
  9. Benzo[i]phenanthridines: TOP1-Targeting Antitumor Agents
    EDMOND LAVOIE; Fiscal Year: 2006
  10. STRUCTURE/FUNCTION OF TWO DNA BINDING PROTEINS
    WILHELMUS HOL; Fiscal Year: 2004

Detail Information

Publications288 found, 100 shown here

  1. ncbi 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
    ..The first class includes changes to residues that contribute to direct interactions with the drug, whereas a second class would alter interactions with the DNA and thereby destabilize the drug-binding site...
  2. ncbi Topoisomerase I inhibitors: camptothecins and beyond
    Yves Pommier
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, 20892 4255, USA
    Nat Rev Cancer 6:789-802. 2006
    ....
  3. ncbi BLAP18/RMI2, a novel OB-fold-containing protein, is an essential component of the Bloom helicase-double Holliday junction dissolvasome
    Thiyam Ramsing Singh
    Division of Experimental Hematology and Cancer Biology, Cincinnati Children s Research Foundation, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229, USA
    Genes Dev 22:2856-68. 2008
    ..Finally, BLAP18/RMI2 stimulates the dHJ resolution capability of the BTB complex. Together, these results establish BLAP18/RMI2 as an essential member of the BTB dHJ dissolvasome that is required for the maintenance of a stable genome...
  4. ncbi Antitumour drugs impede DNA uncoiling by topoisomerase I
    Daniel A Koster
    Kavli Institute of Nanoscience, Faculty of Applied Sciences, Delft University of Technology, Lorentzweg 1, 2628 CJ Delft, The Netherlands
    Nature 448:213-7. 2007
    ..This combination of single-molecule and in vivo data suggests a cytotoxic mechanism for camptothecins, in which the accumulation of positive supercoils ahead of the replication machinery induces potentially lethal DNA lesions...
  5. ncbi Srs2 and Sgs1-Top3 suppress crossovers during double-strand break repair in yeast
    Grzegorz Ira
    Rosenstiel Center and Department of Biology, Brandeis University, Waltham, MA 02454, USA
    Cell 115:401-11. 2003
    ..Srs2 promotes the noncrossover synthesis-dependent strand-annealing (SDSA) pathway, apparently by regulating Rad51 binding during strand exchange...
  6. ncbi Hereditary ataxia SCAN1 cells are defective for the repair of transcription-dependent topoisomerase I cleavage complexes
    Ze Hong Miao
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    DNA Repair (Amst) 5:1489-94. 2006
    ....
  7. ncbi Mechanism of action of eukaryotic DNA topoisomerase I and drugs targeted to the enzyme
    Y Pommier
    Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, Bethesda, MD 20892 4255, USA
    Biochim Biophys Acta 1400:83-105. 1998
    ..Because of the importance of topoisomerase I as a chemotherapeutic target, we review the mechanisms of action of camptothecins and the other topoisomerase I inhibitors identified to date...
  8. ncbi Yeast Tdp1 and Rad1-Rad10 function as redundant pathways for repairing Top1 replicative damage
    John R Vance
    Plantaceutica, Incorporated, P O Box 12060, 99 Alexander Drive, Research Triangle Park, NC 27709 2060, USA
    Proc Natl Acad Sci U S A 99:13669-74. 2002
    ..Finally, we show that yeast lacking the Rad1-Rad10-related proteins Mus81-Mms4 display a unique pattern of camptothecin sensitivity and suggest a concerted model for the action of these endonucleases...
  9. ncbi Clinical applications of the camptothecins
    C H Takimoto
    Developmental Therapeutics Department, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, Building 8, Room 5101, Bethesda Naval Hospital, Bethesda, MD 20892, USA
    Biochim Biophys Acta 1400:107-19. 1998
    ..The successful development of the camptothecins as antitumor agents highlights the importance of topoisomerase I as a target for cancer chemotherapy...
  10. 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 reported cell lines and approaches described in this article provide new tools to perform detailed functional analyses related to Top1 function...
  11. ncbi TDP1 facilitates chromosomal single-strand break repair in neurons and is neuroprotective in vivo
    Sachin Katyal
    Department Genetics and Tumor Cell Biology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
    EMBO J 26:4720-31. 2007
    ..These data indicate that TDP1 is required for neural homeostasis, and reveal a widespread requisite for TDP1 function in response to acutely elevated levels of Top1-associated DNA strand breaks...
  12. ncbi Functional overlap between Sgs1-Top3 and the Mms4-Mus81 endonuclease
    V Kaliraman
    Department of Molecular Biology and Biochemistry Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, New Jersey 08854, USA
    Genes Dev 15:2730-40. 2001
    ..Repair of this double-strand break (DSB) by homologous recombination may be responsible for the elevated levels of sister chromatid exchange (SCE) found in BLM(-/-) cells...
  13. ncbi Repair of topoisomerase I covalent complexes in the absence of the tyrosyl-DNA phosphodiesterase Tdp1
    Chunyan Liu
    Laboratory of Molecular Biology, National Institute of Mental Health, Bethesda, MD 20892 4034, USA
    Proc Natl Acad Sci U S A 99:14970-5. 2002
    ....
  14. ncbi Ubiquitin/26S proteasome-mediated degradation of topoisomerase I as a resistance mechanism to camptothecin in tumor cells
    S D Desai
    Department of Pharmacology, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, New Jersey 08854, USA
    Cancer Res 61:5926-32. 2001
    ....
  15. ncbi Topoisomerase II is a structural component of mitotic chromosome scaffolds
    W C Earnshaw
    J Cell Biol 100:1706-15. 1985
    ..Our results suggest that topoisomerase II may be an enzyme that is also a structural protein of interphase nuclei and mitotic chromosomes...
  16. ncbi Yeast gene for a Tyr-DNA phosphodiesterase that repairs topoisomerase I complexes
    J J Pouliot
    Laboratory of Molecular Biology, National Institute of Mental Health, Building 36, Room 1B08, Bethesda, MD 20892 4034, USA
    Science 286:552-5. 1999
    ..The presence of this gene in humans may have implications for the effectiveness of topoisomerase I poisons, such as the camptothecins, in chemotherapy...
  17. ncbi Resolution of converging replication forks by RecQ and topoisomerase III
    Catherine Suski
    Molecular Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
    Mol Cell 30:779-89. 2008
    ..This resolution reaction is specific for the RecQ-topoisomerase III pair and is mediated by interaction of both of these enzymes with the single-stranded DNA-binding protein SSB...
  18. 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
    ..For the type II topoisomerases, the binding and hydrolysis of ATP further modulate conformational changes in the enzymes to effect changes in DNA topology...
  19. 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
    ..The increase in religation rate of the mutant, explained by means of the enhanced linker flexibility, provides an explanation for the mutant camptothecin resistance...
  20. ncbi DNA gyrase, topoisomerase IV, and the 4-quinolones
    K Drlica
    Public Health Research Institute, New York, New York 10016, USA
    Microbiol Mol Biol Rev 61:377-92. 1997
    ..Thus, quinolone-topoisomerase biology is providing a model for understanding aspects of host-parasite interactions and providing ways to investigate manipulation of the bacterial chromosome by topoisomerases...
  21. ncbi Reconstitution and functional characterization of the unusual bi-subunit type I DNA topoisomerase from Leishmania donovani
    Benu Brata Das
    Department of Molecular Parasitology, Indian Institute of Chemical Biology 4, Raja S.C. Mullick Road, Kolkata 700032, India
    FEBS Lett 565:81-8. 2004
    ..Interaction between the two subunits leading to the formation of an active complex could be explored as an insight for development of new therapeutic agents with specific selectivity...
  22. ncbi Cloning, expression, purification and characterization of DNA topoisomerase I of Mycobacterium tuberculosis
    F Yang
    Department of Medicine, University of Pennsylvania, Philadelphia 19104, USA
    Gene 178:63-9. 1996
    ..Unlike the more well-characterized E. coli Topo I, MTb Topo I does not contain a zinc-finger DNA-binding motif in the C-terminal domain of the protein...
  23. 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
    ..However, the significance of top1 mutations to CPT resistance needs to be further investigated...
  24. ncbi Cloning of the TIS gene suppressed by topoisomerase inhibitors
    Y Onishi
    Department of Biochemistry, Tokyo Dental College, Masago 1 2 2, Mihama ku, Chiba 261 8502, Japan
    Gene 215:453-9. 1998
    ..Considering that topoisomerase I is an essential enzyme in mammalian cells, the TIS protein may have an important role in camptothecin toxicity...
  25. ncbi Schedule-dependent inhibition of hypoxia-inducible factor-1alpha protein accumulation, angiogenesis, and tumor growth by topotecan in U251-HRE glioblastoma xenografts
    Annamaria Rapisarda
    Science Applications International Corporation Frederick, Inc, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA
    Cancer Res 64:6845-8. 2004
    ..These results provide a compelling rationale for testing topotecan in clinical trials to target HIF-1 in cancer patients...
  26. ncbi Defective DNA single-strand break repair in spinocerebellar ataxia with axonal neuropathy-1
    Sherif F El-Khamisy
    Genome Damage and Stability Centre, University of Sussex, Science Park Road, Falmer, Brighton BN1 9RQ, UK
    Nature 434:108-13. 2005
    ..These data identify a defect in SSBR in a neurodegenerative disease, and implicate this process in the maintenance of genetic integrity in post-mitotic neurons...
  27. 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
    ....
  28. ncbi Cloning of cDNA encoding a novel mouse DNA topoisomerase III (Topo IIIbeta) possessing negatively supercoiled DNA relaxing activity, whose message is highly expressed in the testis
    T Seki
    Department of Molecular Cell Biology, Faculty of Pharmaceutical Sciences, Tohoku University, Sendai 980 8578, Japan
    J Biol Chem 273:28553-6. 1998
    ..The levels of TOP3beta mRNA in the testis increased slightly 14 days and considerably 17 days after birth, when the cells in the pachytene phase begin to appear and increase...
  29. ncbi Complete nucleotide sequence of the topA gene encoding Escherichia coli DNA topoisomerase I
    Y C Tse-Dinh
    J Mol Biol 191:321-31. 1986
    ..Mapping of promoters by deletion of sequences upstream from the ATG initiation codon indicates the existence of at least two promoters that direct transcription into topA...
  30. ncbi Replication-mediated DNA damage by camptothecin induces phosphorylation of RPA by DNA-dependent protein kinase and dissociates RPA:DNA-PK complexes
    R G Shao
    Laboratory of Molecular Pharmacology, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 4255, USA
    EMBO J 18:1397-406. 1999
    ..Keywords: camptothecin/DNA damage/DNA-dependent protein kinase/RPA2 phosphorylation..
  31. ncbi Friction and torque govern the relaxation of DNA supercoils by eukaryotic topoisomerase IB
    Daniel A Koster
    Kavli Institute of Nanoscience, Faculty of Applied Sciences, Delft University of Technology, Lorentzweg 1, 2628 CJ Delft, The Netherlands
    Nature 434:671-4. 2005
    ..We propose a model for topoisomerization in which the torque drives the DNA rotation over a rugged periodic energy landscape in which the topoisomerase has a small but quantifiable probability to religate the DNA once per turn...
  32. ncbi A TOPRIM domain in the crystal structure of the catalytic core of Escherichia coli primase confirms a structural link to DNA topoisomerases
    M Podobnik
    Laboratories of Molecular Biophysics, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021, USA
    J Mol Biol 300:353-62. 2000
    ..The catalytic domain of primase is crescent-shaped, and the concave face of the crescent is predicted to accommodate about 10 base-pairs of RNA-DNA duplex in a loose interaction, thereby limiting processivity...
  33. ncbi BLAP75/RMI1 promotes the BLM-dependent dissolution of homologous recombination intermediates
    Leonard Wu
    Cancer Research UK, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom
    Proc Natl Acad Sci U S A 103:4068-73. 2006
    ..Implications of the conserved ability of type IA topoisomerases to catalyze dissolution and how the evolution of factors such as BLAP75/RMI1 might confer specificity on the execution of this process are discussed...
  34. ncbi Pharmacogenomic identification of targets for adjuvant therapy with the topoisomerase poison camptothecin
    Jonathan P Carson
    Department of Genetics and Genomics, Boston University School of Medicine, Boston, Massachusetts, USA
    Cancer Res 64:2096-104. 2004
    ....
  35. ncbi Binding and activation of DNA topoisomerase III by the Rmi1 subunit
    Chi Fu Chen
    Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey 08854, USA
    J Biol Chem 282:28971-9. 2007
    ..These results demonstrate that Top3-Rmi1 functions as a complex and suggest that Rmi1 stimulates Top3 by promoting its interaction with ssDNA...
  36. ncbi Topoisomerase 3alpha and RMI1 suppress somatic crossovers and are essential for resolution of meiotic recombination intermediates in Arabidopsis thaliana
    Frank Hartung
    Botany II, University of Karlsruhe, Karlsruhe, Germany
    PLoS Genet 4:e1000285. 2008
    ....
  37. ncbi Bipartite structure of the SGS1 DNA helicase in Saccharomyces cerevisiae
    J R Mullen
    Department of Molecular Biology and Biochemistry, Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, New Jersey 08855, USA
    Genetics 154:1101-14. 2000
    ..We conclude that the amino terminus of Sgs1 has an essential role in SGS1 function, distinct from that of the DNA helicase, with which it genetically interacts...
  38. ncbi Structures of three classes of anticancer agents bound to the human topoisomerase I-DNA covalent complex
    Bart L Staker
    deCODE BioStructures, 7869 NE Day Road West, Bainbridge Island, Washington 98110, USA
    J Med Chem 48:2336-45. 2005
    ..These new X-ray structures explain how very different molecules can stabilize top1-DNA covalent complexes and will aid the rational design of completely novel structural classes of anticancer drugs...
  39. ncbi Mutations in homologous recombination genes rescue top3 slow growth in Saccharomyces cerevisiae
    Erika Shor
    Department of Genetics and Development, Columbia University College of Physicians and Surgeons, New York, New York 10032 2704, USA
    Genetics 162:647-62. 2002
    ..We present a model wherein Rad51 helps recruit Sgs1-Top3 to sites of replicative damage...
  40. ncbi Irinotecan: mechanisms of tumor resistance and novel strategies for modulating its activity
    Y Xu
    Department of Medicine and the Experimental Therapeutics Program, Comprehensive Cancer Center, Arthur G. James Cancer Hospital, Columbus, OH, USA
    Ann Oncol 13:1841-51. 2002
    ....
  41. ncbi The role of the DNA mismatch repair system in the cytotoxicity of the topoisomerase inhibitors camptothecin and etoposide to human colorectal cancer cells
    S Jacob
    , Institut Gustave Roussy, 94 800 Villejuif, France
    Cancer Res 61:6555-62. 2001
    ..Interestingly, our observations provide the rationale for the better responsiveness of MSI+ tumors to CPT-11, a camptothecin derivative, which we have observed in patients with metastatic colorectal cancers...
  42. ncbi Therapeutic activity of CPT-11, a DNA-topoisomerase I inhibitor, against peripheral primitive neuroectodermal tumour and neuroblastoma xenografts
    G Vassal
    Department of Pediatric Oncology, Institut Gustave Roussy, Villejuif, France
    Br J Cancer 74:537-45. 1996
    ..In conclusion, CPT-11 demonstrated significant activity against pPNET and neuroblastoma xenografts. Further clinical development of CPT-11 in paediatric oncology is warranted...
  43. ncbi Phase III comparison of two irinotecan dosing regimens in second-line therapy of metastatic colorectal cancer
    Charles S Fuchs
    Dana Farber Cancer Institute, Boston, MA 02115, USA
    J Clin Oncol 21:807-14. 2003
    ..We prospectively compared the efficacy and tolerability of two irinotecan regimens (once a week for 4 weeks followed by a 2-week rest period [weekly] v once every 3 weeks) in such patients...
  44. ncbi Isodiospyrin as a novel human DNA topoisomerase I inhibitor
    Chun-Yuan Ting
    Institute of Biochemistry, School of Life Science, National Yang Ming University, Taipei, Taiwan
    Biochem Pharmacol 66:1981-91. 2003
    ..Thus, these findings have important implications on naphthoquinone and its derivatives' cellular mode of actions, i.e. these novel DNA topoisomerase I inhibitors can prevent both DNA relaxation and kinase activities of htopo I...
  45. ncbi Werner protein stimulates topoisomerase I DNA relaxation activity
    Jean-Philippe Laine
    Laboratory of Molecular Gerontology, National Institute on Aging/NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA
    Cancer Res 63:7136-46. 2003
    ..Our data provide new insight into the interrelationship between RecQ helicases and topoisomerases in the maintenance of genomic integrity and prevention of tumorigenesis...
  46. ncbi Studies of a positive supercoiling machine. Nucleotide hydrolysis and a multifunctional "latch" in the mechanism of reverse gyrase
    A Chapin Rodriguez
    Medical Research Council Laboratory of Molecular Biology, Hills Rd, Cambridge CB2 2QH, United Kingdom
    J Biol Chem 277:29865-73. 2002
    ..This suggests that the mechanism of reverse gyrase is best described by a combination of recently proposed models...
  47. ncbi Mitotic chromosome condensation in the rDNA requires TRF4 and DNA topoisomerase I in Saccharomyces cerevisiae
    I B Castaño
    Department of Radiation Oncology, University of California, San Francisco 94143, USA
    Genes Dev 10:2564-76. 1996
    ..These data indicate that TOP1 (encoding topo I) and TRF4 participate in overlapping or dependent steps in mitotic chromosome condensation and serve to define a previously unrecognized biological function of topo I...
  48. ncbi The Bloom's syndrome helicase suppresses crossing over during homologous recombination
    Leonard Wu
    Cancer Research UK, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK
    Nature 426:870-4. 2003
    ..These results have wider implications for our understanding of the process of homologous recombination and the mechanisms that exist to prevent tumorigenesis...
  49. ncbi Protein concerted motions in the DNA-human topoisomerase I complex
    Giovanni Chillemi
    CASPUR, c/o University of Rome La Sapienza, P. le Aldo Moro 5, 00185 Rome, Italy
    Nucleic Acids Res 31:1525-35. 2003
    ..The motion of specific residues has also been found to explain the effect of single point mutations that make topo I resistant to the anticancer drug camptothecin...
  50. ncbi Escherichia coli DNA topoisomerase I mutants have compensatory mutations in DNA gyrase genes
    S DiNardo
    Cell 31:43-51. 1982
    ..An excess of negative supercoils due to an absence of topoisomerase I is deleterious to the cell, but a moderate gyrase deficiency is not harmful...
  51. ncbi Biochemical characterization of an invariant histidine involved in Escherichia coli DNA topoisomerase I catalysis
    Kay Perry
    Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, 2153 Sheridan Road, Evanston, IL 60208, USA
    J Biol Chem 277:13237-45. 2002
    ..These observations indicate that His-365 participates in DNA binding and is responsible for optimal catalysis at physiological pH...
  52. ncbi Correlation of serum anti-DNA topoisomerase I antibody levels with disease severity and activity in systemic sclerosis
    Paul Q Hu
    University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    Arthritis Rheum 48:1363-73. 2003
    ..001) and IgA (P < 0.05) titers than did those with inactive disease. CONCLUSION: Serum levels of anti-topo I antibody correlate positively with disease severity and disease activity in SSc...
  53. ncbi Reverse gyrase: an unusual DNA manipulator of hyperthermophilic organisms
    Mose Rossi
    Institute of Protein Biochemistry, Consiglio Nazionale delle Ricerche, Naples, Italy
    Ital J Biochem 56:103-9. 2007
    ..We review here recent phylogenetic, biochemical and structural data on reverse gyrase and discuss the possible role of this enzyme in the biology of hyperthermophilic organisms...
  54. ncbi Clinical significance of anti-topoisomerase I antibody levels determined by ELISA in systemic sclerosis
    S Sato
    Department of Dermatology, Kanazawa University School of Medicine, Kanazawa, Ishikawa, Japan
    Rheumatology (Oxford) 40:1135-40. 2001
    ..CONCLUSIONS: These results suggest the potential clinical significance of anti-topo I antibody levels in evaluating disease severity and the prognosis in SSc...
  55. ncbi A physiological role for DNA supercoiling in the osmotic regulation of gene expression in S. typhimurium and E. coli
    C F Higgins
    Department of Biochemistry, University of Dundee, Scotland
    Cell 52:569-84. 1988
    ....
  56. 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
    ....
  57. ncbi Persistence of camptothecin analog-topoisomerase I-DNA ternary complexes: a molecular dynamics study
    Fung Ming Siu
    Department of Chemistry and Open Laboratory of Chemical Biology of the Institute of Molecular Technology for Drug Discovery and Synthesis, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China
    J Am Chem Soc 130:17928-37. 2008
    ....
  58. ncbi SGS1, a homologue of the Bloom's and Werner's syndrome genes, is required for maintenance of genome stability in Saccharomyces cerevisiae
    P M Watt
    Imperial Cancer Research Fund Laboratories, University of Oxford, John Radcliffe Hospital, United Kingdom
    Genetics 144:935-45. 1996
    ..This contrasts with the telomere maintenance defects of Werner's patients. We conclude that the SGS1 gene product is involved in the maintenance of genome stability in S. cerevisiae...
  59. ncbi Reverse gyrase recruitment to DNA after UV light irradiation in Sulfolobus solfataricus
    Alessandra Napoli
    Institute of Protein Biochemistry, Consiglio Nazionale delle Ricerche, Via P. Castellino 111, 80131 Naples, Italy
    J Biol Chem 279:33192-8. 2004
    ..Our results suggest a general role of the association of such activities in maintaining genome integrity and a mutual effect of DNA topology and repair...
  60. ncbi Transcriptional consequences of topoisomerase inhibition
    I Collins
    Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1500, USA
    Mol Cell Biol 21:8437-51. 2001
    ..The results have ramifications for the use of these drugs as antineoplastic agents...
  61. ncbi M phase-specific association of human topoisomerase IIIbeta with chromosomes
    M Kobayashi
    Department of Chemistry, College of Science, Rikkyo St Paul s University, 3 34 1 Nishi Ikebukuro, Toshima ku, Tokyo 171 8501, Japan
    Biochem Biophys Res Commun 287:282-7. 2001
    ..The GFP fusion of the isoform 2 was found in the cytoplasm, indicating the nuclear localization signal sequence in the isoform 1 is in the C-terminal part that is different between the two isoforms...
  62. ncbi Roles of topoisomerases in maintaining steady-state DNA supercoiling in Escherichia coli
    E L Zechiedrich
    Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA
    J Biol Chem 275:8103-13. 2000
    ..09), greatly stimulating transcription from the supercoiling sensitive leu-500 promoter and increasing the number of supercoils trapped by lambda integrase site-specific recombination...
  63. ncbi Disease subsets, antinuclear antibody profile, and clinical features in 127 French and 247 US adult patients with systemic sclerosis
    Olivier C Meyer
    Rheumatology Unit, Bichat Hospital, Paris, France
    J Rheumatol 34:104-9. 2007
    ..To investigate the specificities of antinuclear antibodies (ANA) associated with systemic sclerosis (SSc) disease classification and internal organ involvement among patients with SSc of different origins (European and American)...
  64. ncbi Immunohistochemical staining for DNA topoisomerase I, DNA topoisomerase II-alpha and p53 in gastric carcinomas
    L W Coleman
    Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA
    Anticancer Res 21:1167-72. 2001
    ..Of the 22 cases of gastric carcinoma, 8 (36%) had high levels of topo I, a large number of cycling tumor cells and normal p53 expression. These are the molecular parameters that might suggest responsiveness to drugs targeting topo I...
  65. ncbi Structural studies of E. coli topoisomerase III-DNA complexes reveal a novel type IA topoisomerase-DNA conformational intermediate
    Anita Changela
    Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, 2205 Tech Drive, Evanston, IL 60208, USA
    J Mol Biol 368:105-18. 2007
    ..Comparative analysis of the various conformational states suggests a sequence of domain movements undertaken by the enzyme upon substrate binding...
  66. ncbi Function of DNA topoisomerases as replication swivels in Saccharomyces cerevisiae
    R A Kim
    Department of Biochemistry and Molecular Biology, Harvard University, Cambridge, MA 02138
    J Mol Biol 208:257-67. 1989
    ..The patterns of DNA synthesis in asynchronously grown delta top1 top2 ts cells at permissive and non-permissive temperatures are also consistent with the above conclusions...
  67. ncbi In vitro synergistic interactions between the cisplatin analogue nedaplatin and the DNA topoisomerase I inhibitor irinotecan and the mechanism of this interaction
    F Kanzawa
    Pharmacology Division, National Cancer Center Research Institute, Tokyo, Japan
    Clin Cancer Res 7:202-9. 2001
    ..These biochemical interactions might be responsible for the synergistic interaction between NDP and CPT-11. These results suggest that the combination of NDP with CPT-11 may be clinically useful for the chemotherapy of lung cancer...
  68. ncbi Two different schedules of irinotecan (CPT-11) in patients with advanced colorectal carcinoma relapsing after a 5-fluorouracil and leucovorin combination. A randomized study
    N Tsavaris
    Oncology Unit, Department of Pathophysiology, Laikon General Hospital, University of Athens School of Medicine, 11527 Athens, Greece
    Cancer Chemother Pharmacol 52:514-9. 2003
    ..To evaluate the efficacy and safety of irinotecan as second-line treatment in patients with advanced colorectal cancer (ACC) failing or relapsing after 5-fluorouracil (5-FU) plus leucovorin (LV) standard chemotherapy...
  69. ncbi A hot story from comparative genomics: reverse gyrase is the only hyperthermophile-specific protein
    Patrick Forterre
    Institut de Genetique et Microbiologie, CNRS UMR 8621, Bat 409, Universite Paris Sud, 91405 Orsay Cedex, France
    Trends Genet 18:236-7. 2002
    ..This result emphasizes the importance of reverse gyrase in the adaptation of life to very high temperatures, and strengthens the idea that evolution of this enzyme was crucial in the origin of hyperthermophiles...
  70. ncbi Bloom helicase and DNA topoisomerase IIIalpha are involved in the dissolution of sister chromatids
    Masayuki Seki
    Molecular Cell Biology Laboratory, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba 6 3, Aramaki, Aoba ku, Sendai 980 8578, Japan
    Mol Cell Biol 26:6299-307. 2006
    ..Taken together with the biochemical properties of BLM and Top3alpha, these data indicate that BLM and Top3alpha execute the dissolution of sister chromatids...
  71. ncbi Adenosine 5'-O-(3-thio)triphosphate (ATPgammaS) promotes positive supercoiling of DNA by T. maritima reverse gyrase
    Stefan P Jungblut
    University of Basel, Biozentrum, Dept of Biophysical Chemistry, Klingelbergstrasse 70, CH 4056 Basel, Switzerland
    J Mol Biol 371:197-209. 2007
    ....
  72. ncbi More complexity to the Bloom's syndrome complex
    Yilun Liu
    Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    Genes Dev 22:2737-42. 2008
    ..RMI2 may be a representative of a new family of OB-fold-containing proteins that are important for complex stabilization and checkpoint response...
  73. ncbi DNA sequence selectivity of topoisomerases and topoisomerase poisons
    G Capranico
    Division of Experimental Oncology B, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133 Milan, Italy
    Biochim Biophys Acta 1400:185-94. 1998
    ..The complete definition of the diverse pharmacophores of topoisomerase II poisons will certainly be of value for the design of new agents directed to specific genomic sites, and more effective in the treatment of human cancer...
  74. ncbi Human RecQ5beta, a large isomer of RecQ5 DNA helicase, localizes in the nucleoplasm and interacts with topoisomerases 3alpha and 3beta
    A Shimamoto
    AGENE Research Institute, 200 Kajiwara Kamakura, Kanagawa 247 0063, Japan
    Nucleic Acids Res 28:1647-55. 2000
    ..These results predict that RecQ5beta may have an important role in DNA metabolism and may also be related to a distinct genetic disease...
  75. ncbi An RNA topoisomerase
    H Wang
    Department of Chemistry, New York University, NY 10003, USA
    Proc Natl Acad Sci U S A 93:9477-82. 1996
    ..The conversion of circles to knots is accompanied by a small amount of RNA catenane generation. These findings suggest that strand passage must be considered a potential component of the folding and modification of RNA structures...
  76. ncbi A two-subunit type I DNA topoisomerase (reverse gyrase) from an extreme hyperthermophile
    R Krah
    Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 93:106-10. 1996
    ..The appearance of this unique structure in a highly conserved enzyme family supports the hypothesis that the methanogens branched from other prokaryotes and eukaryotes very early in evolution...
  77. 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 structures also lead to the proposal that the topoisomerization step occurs by a mechanism termed "controlled rotation."..
  78. ncbi Studies of sequence-specific DNA binding, DNA cleavage, and topoisomerase I inhibition by the dimeric chromomycin A3 complexed with Fe(II)
    Ming Hon Hou
    Biotechnology Center, National Chung Hsing University, Taichung, 402 Taiwan
    Biochemistry 47:5493-502. 2008
    ..Our results provide significant evidence that the [(Chro)2-Fe(II)] complex could be promising in terms of its biological applications in the future...
  79. ncbi Topoisomerase I protein expression in primary colorectal cancer and recurrences after 5-FU-based adjuvant chemotherapy
    P Gouveris
    Medical Oncology Unit, Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece
    J Cancer Res Clin Oncol 133:1011-5. 2007
    ..Our aim was to investigate whether chemotherapy with 5-FU induces an alteration in the levels of topoisomerase I (topo I) in colorectal neoplastic tissues..
  80. ncbi A poxvirus-like type IB topoisomerase family in bacteria
    Berit Olsen Krogh
    Molecular Biology Program, Sloan-Kettering Institute, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 99:1853-8. 2002
    ..Remarkably, bacteria that possess topoisomerase IB appear to lack DNA topoisomerase III...
  81. ncbi DNA supercoiling and temperature adaptation: A clue to early diversification of life?
    P Lopez-Garcia
    Institut de Genetique et Microbiologie, Universite Paris Sud, Bat 409, 91405 Orsay Cedex, France
    J Mol Evol 49:439-52. 1999
    ..Some mesophilic archaea would have improved their adaptability to mesophily by importing gyrase from bacteria...
  82. ncbi [Therapeutic approach for colorectal cancer with topoisomerase as a molecular target]
    Takuya Tsunoda
    Department of Surgery and Bioengineering, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo
    Nippon Rinsho 61:472-5. 2003
  83. ncbi Anthocyanidins modulate the activity of human DNA topoisomerases I and II and affect cellular DNA integrity
    Michael Habermeyer
    Department of Chemistry, Division of Food Chemistry and Environmental Toxicology, University of Kaiserslautern, Erwin-Schroedinger Strasse 52, 67663 Kaiserslautern, Germany
    Chem Res Toxicol 18:1395-404. 2005
    ..These data indicate substantial affinity to double-stranded DNA, which might contribute at least to the DNA strand breaking effect of anthocyanidins at higher concentrations (> or = 50 microM)...
  84. ncbi Clinical trials using irinotecan
    Peter J Houghton
    Department of Molecular Pharmacology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA
    J Pediatr Hematol Oncol 24:84-5. 2002
  85. ncbi Antitumor agents 216. Synthesis and evaluation of paclitaxel-camptothecin conjugates as novel cytotoxic agents
    Hironori Ohtsu
    Natural Products Laboratory, School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    Bioorg Med Chem 11:1851-7. 2003
    ....
  86. ncbi Pooled analysis of phase II window studies in children with contemporary high-risk metastatic rhabdomyosarcoma: a report from the Soft Tissue Sarcoma Committee of the Children's Oncology Group
    Joanne J Lager
    Duke University Medical Center, Durham, NC 27710, USA
    J Clin Oncol 24:3415-22. 2006
    ..Finally, these results provide a rationale for incorporating ifosfamide, etoposide, doxorubicin, and topoisomerase I poisons in future trials of high-risk metastatic rhabdomyosarcoma...
  87. ncbi Platinated DNA adducts enhance poisoning of DNA topoisomerase I by camptothecin
    Robert C A M van Waardenburg
    Department of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    J Biol Chem 279:54502-9. 2004
    ..These results indicate that the cytotoxic activity of cisplatin is due, in part, to poisoning of Top1, which is exacerbated in the presence of topotecan...
  88. ncbi Gene expression profiles as biomarkers for the prediction of chemotherapy drug response in human tumour cells
    Amadeo M Parissenti
    Tumour Biology Research Program, Sudbury Regional Hospital, Department of Biology, Laurentian University, Sudbury, Ottawa, Ontario, Canada
    Anticancer Drugs 18:499-523. 2007
    ..Genetic predictors of response to a variety of anticancer agents are discussed, including the anthracyclines, taxanes, topoisomerase I and II inhibitors, nucleoside analogs, alkylating agents, and vinca alkaloids...
  89. ncbi Camptothecins and topoisomerase I: a foot in the door. Targeting the genome beyond topoisomerase I with camptothecins and novel anticancer drugs: importance of DNA replication, repair and cell cycle checkpoints
    Yves Pommier
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA
    Curr Med Chem Anticancer Agents 4:429-34. 2004
    ..Furthermore, targeting DNA repair (Tdp1) and checkpoints (ATM, Chk1 and Chk2) might increase the selectivity of Top1 inhibitors for tumors, thereby increasing the antitumor activity while reducing the side effects of Top1 inhibitors...
  90. ncbi Inhibition of Flp recombinase by the topoisomerase I-targeting drugs, camptothecin and NSC-314622
    R F Frøhlich
    Department of Molecular and Structural Biology, University of Aarhus, Building 130, C F Møllers Alle, DK 8000 Aarhus C, Denmark
    J Biol Chem 276:6993-7. 2001
    ..The results suggest that Flp and other Int family recombinases may provide model systems for dissecting the molecular mechanisms of topoisomerase I-directed anti-cancer therapeutic agents...
  91. ncbi Topoisomerase I inhibitors in the treatment of head and neck cancer
    B A Murphy
    Vanderbilt University, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee 37232, USA
    Oncology (Williston Park) 15:47-52. 2001
    ..9%), with a median survival of 214 days and a 1-year survival rate of 30.2%. The response and toxicity appear to be dose dependent. Further investigation of irinotecan in combination with other active agents and radiotherapy is warranted...
  92. ncbi Pharmacology of topoisomerase I inhibitors irinotecan (CPT-11) and topotecan
    Ron H J Mathijssen
    Department of Medical Oncology, Rotterdam Cancer Institute Daniel den Hoed Kliniek and University Hospital Rotterdam, PO Box 5201, Rotterdam, 3008 AE, The Netherlands
    Curr Cancer Drug Targets 2:103-23. 2002
    ....
  93. ncbi Topoisomerase poisons differentially activate DNA damage checkpoints through ataxia-telangiectasia mutated-dependent and -independent mechanisms
    Wai Yi Siu
    Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong
    Mol Cancer Ther 3:621-32. 2004
    ..These data indicate that the involvement of ATM following treatment with Topo poisons differs extensively with dosage and for different cell cycle checkpoints...
  94. ncbi DNA damage induced by DNA topoisomerase I- and topoisomerase II-inhibitors detected by histone H2AX phosphorylation in relation to the cell cycle phase and apoptosis
    Xuan Huang
    Brander Cancer Research Institute, New York Medical College, Valhalla, New York, USA
    Cell Cycle 2:614-9. 2003
    ..The data also indicate that regardless whether treated with inhibitors of topo1 or topo2, at comparable levels of dsDNA breaks, the cells replicating DNA have a higher proclivity to undergo apoptosis compared to G1 or G2/M cells...
  95. ncbi Inhibitory properties of antitumor prostaglandins against topoisomerases
    Keitarou Suzuki
    Laboratory of Pharmaceutical Microbiology, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan
    Biosci Biotechnol Biochem 66:1706-12. 2002
    ..Delta12,14-PGJ2 differentially inhibited topo I from different sources. Delta12,14-PGJ2 was a topo inhibitor of the cleavable complex-nonforming type without DNA intercalation...
  96. ncbi Roles of NF-kappaB and 26 S proteasome in apoptotic cell death induced by topoisomerase I and II poisons in human nonsmall cell lung carcinoma
    M Tabata
    Experimental Therapeutics Program, Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Biol Chem 276:8029-36. 2001
    ..In summary, apoptosis induced by topoisomerase poisons in NSCLC cells is not mediated by NF-kappaB but can be manipulated by proteasome inhibitors...
  97. ncbi The novel poly(ADP-Ribose) polymerase inhibitor, AG14361, sensitizes cells to topoisomerase I poisons by increasing the persistence of DNA strand breaks
    Lisa M Smith
    Northern Institute for Cancer Research and Institute for Cell and Molecular Biosciences, Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom
    Clin Cancer Res 11:8449-57. 2005
    ..Therefore, the most likely mechanism for the potentiation of topo I poison-mediated cytotoxicity by AG14361 is via PARP-1-dependent base excision repair...
  98. ncbi Radiation enhancement by the combined use of topoisomerase I inhibitors, RFS-2000 or CPT-11, and topoisomerase II inhibitor etoposide in human lung cancer cells
    Jae Sung Kim
    Department of Radiation Oncology, The Vanderbilt Clinic B-902, Vanderbilt University Medical Center, 1301 22nd Avenue S, Nashville, TN 37232-5671, USA
    Radiother Oncol 62:61-7. 2002
    ..The mechanism of radiation enhancement may involve inhibition of SLDR with RFS-2000 plus etoposide, but other mechanisms may be involved in the combined treatment including CPT-11...
  99. ncbi 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
    ....
  100. ncbi 2070-DTI, a topoisomerase inhibitor produced by Streptomyces sp. strain No. 2070
    Keitarou Suzuki
    Department of Pharmaceutical Microbiology, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan
    J Enzyme Inhib Med Chem 18:497-503. 2003
    ..2070-DTI is an inhibitor belonging to the cleavable complex-nonforming type without DNA intercalation...
  101. ncbi Pattern of antitumor activity of a novel camptothecin, ST1481, in a large panel of human tumor xenografts
    Graziella Pratesi
    Istituto Nazionale Tumori, 20133 Milan, Italy
    Clin Cancer Res 8:3904-9. 2002
    ..Based on its therapeutic efficacy in a human non-small cell lung carcinoma model and its favorable pharmacological profile, the novel analogue was selected for further preclinical development...

Research Grants87

  1. Improving CPT-11 Efficacy Using Structural Biology
    MATTHEW REDINBO; Fiscal Year: 2007
    ..2- 2 Description, ..
  2. STRUCTURE/FUNCTION OF TWO DNA BINDING PROTEINS
    WILHELMUS HOL; Fiscal Year: 1999
    ..In addition, the crystal structure of human topoisomerase I will form an excellent basis for the design of new inhibitors which ar potential new cancer drugs. ..
  3. MECHANISM OF ACTION OF ANTITUMOR DRUGS
    Leroy F Liu; Fiscal Year: 2010
    ....
  4. Novel Direct Approaches Toward Bioactive Heterocycles
    Vladimir Gevorgyan; Fiscal Year: 2010
    ....
  5. SAR OF NOVEL TOPO I INHIBITOR AGAINST PROSTATE CANCER
    YUE WEI LEE; Fiscal Year: 2001
    ..abstract_text> ..
  6. ROLE OF TOPOISOMERASES IN DNA REPLICATION
    KENNETH MARIANS; Fiscal Year: 1990
    ....
  7. Anti-Cancer Drug Design Targeting Human Topoisomerase I
    Lance Stewart; Fiscal Year: 2002
    ..The most promising compounds will be examined for their efficacy in stopping human tumor growth in the mouse xenotransplant model. PROPOSED COMMERCIAL APPLICATION: Not available ..
  8. Novel Mechanisms by which RAD18 and POLZ affect Response to Anticancer Agents
    CHRISTINE ELIZABETH CANMAN; Fiscal Year: 2010
    ....
  9. Benzo[i]phenanthridines: TOP1-Targeting Antitumor Agents
    EDMOND LAVOIE; Fiscal Year: 2006
    ....
  10. STRUCTURE/FUNCTION OF TWO DNA BINDING PROTEINS
    WILHELMUS HOL; Fiscal Year: 2004
    ..tuberculosis), and (iii) the most devastating eukaryotic parasite (P. falciparum) known. The latter two account for roughly five million deaths per year worldwide. ..
  11. VACCINIA VIRUS DNA TOPOISOMERASE I
    Stewart Shuman; Fiscal Year: 1993
    ..The third approach, genetically based, will be to isolate virus mutants affected conditionally in DNA topoisomerase activity so as to understand more fully the physiologic role of this enzyme in vivo...
  12. The meiotic role of dtopors in male Drosophila
    JOHN TOMKIEL; Fiscal Year: 2007
    ..This proposal aims to characterize dtopors functions in male meiosis, where it is particularly critical and is required for meiotic chromosome segregation, towards understanding of analogous roles of human Topors in tumor suppression. ..
  13. Bacterial cell killing by topoisomerase I mediated DNA lesion
    Yuk Ching Tse Dinh; Fiscal Year: 2007
    ..Future terrorist attacks employing bacterial pathogens could involve agents resistant to current antibiotics. This research has the potential to lead to the discovery of a novel class of antibiotics. ..
  14. Bacterial cell killing by topoisomerase I mediated DNA lesion
    Yuk Ching Tse Dinh; Fiscal Year: 2010
    ..Future terrorist attacks employing bacterial pathogens could involve agents resistant to current antibiotics. This research has the potential to lead to the discovery of a novel class of antibiotics. ..
  15. New determinants of the DNA damage response in the fission yeast S. pombe
    MATTHEW J O apos CONNELL; Fiscal Year: 2010
    ..Because these processes are ancient in origin, we use simple yeast cells to identify new genes that are relevant to human disease. Our proposal analyses three new genes in the response of cells to DNA damage. ..
  16. Improving CPT-11 Efficacy Using Structural Biology
    MATTHEW REDINBO; Fiscal Year: 2006
    ..5. Assess the efficacy of drug activation and the ability to sensitize cells expressing mutant forms of rCE, hCE1 and hiCE to CPT-11. ..
  17. Improving CPT-11 Efficacy Using Structural Biology
    MATTHEW REDINBO; Fiscal Year: 2003
    ..5. Assess the efficacy of drug activation and the ability to sensitize cells expressing mutant forms of rCE, hCE1 and hiCE to CPT-11. ..
  18. HEPADNAVIRUS ASSOCIATED HEPATOCELLULAR CARCINOMA
    CHARLES ROGLER; Fiscal Year: 1993
    ..This experiment will increase our general understanding of a possible tumor suppressor, or cancer protective, role of gene imprinting...
  19. ROLE OF TOPOISOMERASES IN DNA METABOLISM
    KENNETH MARIANS; Fiscal Year: 1993
    ....
  20. Role of c-Met in SCLC and Potential for Novel Therapy
    Ravi Salgia; Fiscal Year: 2009
    ..Ultimately, we propose to bring to fruition combination therapies using these molecules. ..
  21. Role of c-Met in SCLC and Potential for Novel Therapy
    Ravi Salgia; Fiscal Year: 2010
    ..In the nucleus, it binds to different proteins such as Pax5 and topoisomerase-I, and the studies proposed will dissect out mechanisms for this. Ultimately, we propose to bring to fruition combination therapies using these molecules. ..
  22. Role of c-Met in SCLC and Potential for Novel Therapy
    Ravi Salgia; Fiscal Year: 2009
    ..In the nucleus, it binds to different proteins such as Pax5 and topoisomerase-I, and the studies proposed will dissect out mechanisms for this. Ultimately, we propose to bring to fruition combination therapies using these molecules. ..
  23. Selective Inhibitors to Improve CPT-11 Therapy
    PHILIP POTTER; Fiscal Year: 2007
    ..Additionally, such compounds may allow dose intensification of CPT-11 for improved cancer therapy. ..
  24. Novel Indenoisoquinoline Topoisomerase I Inhibitors
    Mark Cushman; Fiscal Year: 2007
    ..The mechanism of action of the indenoisoquinolines will be studied in detail, and the information will be used to maximize their therapeutic potential as anticancer agents. ..