JAMES CHAMPOUX

Summary

Affiliation: University of Washington
Country: USA

Publications

  1. ncbi request reprint Structure-based analysis of the effects of camptothecin on the activities of human topoisomerase I
    J J Champoux
    Department of Microbiology, Box 357242, University of Washington, Seattle, Washington 98195 7242, USA
    Ann N Y Acad Sci 922:56-64. 2000
  2. ncbi request reprint 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
  3. ncbi request reprint A first view of the structure of a type IA topoisomerase with bound DNA
    James J Champoux
    Dept of Microbiology, Box 357242, School of Medicine, University of Washington, Seattle, WA 98195, USA
    Trends Pharmacol Sci 23:199-201. 2002
  4. pmc Type IA DNA topoisomerases: strictly one step at a time
    James J Champoux
    Department of Microbiology, Box 357242, School of Medicine, University of Washington, Seattle, WA 98195 7242, USA
    Proc Natl Acad Sci U S A 99:11998-2000. 2002
  5. pmc Ribonuclease H: properties, substrate specificity and roles in retroviral reverse transcription
    James J Champoux
    Department of Microbiology, University of Washington, Seattle, WA 98195, USA
    FEBS J 276:1506-16. 2009
  6. ncbi request reprint The crystal structure of human tyrosyl-DNA phosphodiesterase, Tdp1
    Douglas R Davies
    Department of Biochemistry, Box 357742, University of Washington, Seattle, WA 98195, USA
    Structure 10:237-48. 2002
  7. pmc DNA relaxation by human topoisomerase I occurs in the closed clamp conformation of the protein
    James F Carey
    Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 100:5640-5. 2003
  8. ncbi request reprint Requirements for DNA unpairing during displacement synthesis by HIV-1 reverse transcriptase
    Jamie Winshell
    Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195 7242, USA
    J Biol Chem 279:52924-33. 2004
  9. ncbi request reprint Effects of unpaired nucleotides within HIV-1 genomic secondary structures on pausing and strand transfer
    Christian Lanciault
    Department of Microbiology, University of Washington School of Medicine, Seattle, Washington 98195, USA
    J Biol Chem 280:2413-23. 2005
  10. pmc Human Tdp1 cleaves a broad spectrum of substrates, including phosphoamide linkages
    Heidrun Interthal
    Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington 98195 7242, USA
    J Biol Chem 280:36518-28. 2005

Research Grants

  1. PLUS-STRAND PRIMING AND INTEGRATION BY M-MULV & HIV
    JAMES CHAMPOUX; Fiscal Year: 1993
  2. DNA BINDING BY HUMAN TOPOISOMERASE I
    JAMES CHAMPOUX; Fiscal Year: 2003
  3. ENZYMOLOGY OF M MULV AND HIV REPLICATION
    JAMES CHAMPOUX; Fiscal Year: 2004
  4. EUKARYOTIC TOPOISOMERASE I
    JAMES CHAMPOUX; Fiscal Year: 2005
  5. The Enzymology of M-MuLV and HIV Replication
    JAMES CHAMPOUX; Fiscal Year: 2007
  6. EUKARYOTIC TOPOISOMERASE I
    JAMES CHAMPOUX; Fiscal Year: 2007
  7. The Enzymology of M-MuLV and HIV Replication
    JAMES CHAMPOUX; Fiscal Year: 2009
  8. EUKARYOTIC TOPOISOMERASE I
    JAMES CHAMPOUX; Fiscal Year: 2001
  9. EUKARYOTIC TOPOISOMERASE I
    James J Champoux; Fiscal Year: 2010

Collaborators

  • Thomas G Fazzio
  • JAMES STIVERS
  • Adeel Mushtaq
  • Sharon J Schultz
  • Douglas R Davies
  • Heidrun Interthal
  • Zheng Yang
  • Christian Lanciault
  • Miaohua Zhang
  • Wim G J Hol
  • James F Carey
  • Hyeongnam Kim
  • John B Leppard
  • Jamie Winshell
  • Rupa Roy
  • Rhone Akee
  • John H Cardellina
  • Hong Jing Chen
  • Benjamin A Paulson
  • Ben D Buelow
  • Paulene M Quigley
  • Pamela Trowbridge
  • Daniel T Simmons
  • Lisa Sisson

Detail Information

Publications29

  1. ncbi request reprint Structure-based analysis of the effects of camptothecin on the activities of human topoisomerase I
    J J Champoux
    Department of Microbiology, Box 357242, University of Washington, Seattle, Washington 98195 7242, USA
    Ann N Y Acad Sci 922:56-64. 2000
    ..In addition, CPT has been shown to inhibit plasmid DNA relaxation in vitro. The structural bases for these two activities of CPT are explored in relation to the recently published crystal structure of the enzyme with bound DNA...
  2. ncbi request reprint 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...
  3. ncbi request reprint A first view of the structure of a type IA topoisomerase with bound DNA
    James J Champoux
    Dept of Microbiology, Box 357242, School of Medicine, University of Washington, Seattle, WA 98195, USA
    Trends Pharmacol Sci 23:199-201. 2002
    ....
  4. pmc Type IA DNA topoisomerases: strictly one step at a time
    James J Champoux
    Department of Microbiology, Box 357242, School of Medicine, University of Washington, Seattle, WA 98195 7242, USA
    Proc Natl Acad Sci U S A 99:11998-2000. 2002
  5. pmc Ribonuclease H: properties, substrate specificity and roles in retroviral reverse transcription
    James J Champoux
    Department of Microbiology, University of Washington, Seattle, WA 98195, USA
    FEBS J 276:1506-16. 2009
    ....
  6. ncbi request reprint The crystal structure of human tyrosyl-DNA phosphodiesterase, Tdp1
    Douglas R Davies
    Department of Biochemistry, Box 357742, University of Washington, Seattle, WA 98195, USA
    Structure 10:237-48. 2002
    ..The structure also suggests how the unusual protein-DNA substrate binds and provides insights about the nature of the substrate in vivo...
  7. pmc DNA relaxation by human topoisomerase I occurs in the closed clamp conformation of the protein
    James F Carey
    Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195, USA
    Proc Natl Acad Sci U S A 100:5640-5. 2003
    ..These results indicate that DNA relaxation likely proceeds without extensive opening of the enzyme clamp...
  8. ncbi request reprint Requirements for DNA unpairing during displacement synthesis by HIV-1 reverse transcriptase
    Jamie Winshell
    Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195 7242, USA
    J Biol Chem 279:52924-33. 2004
    ....
  9. ncbi request reprint Effects of unpaired nucleotides within HIV-1 genomic secondary structures on pausing and strand transfer
    Christian Lanciault
    Department of Microbiology, University of Washington School of Medicine, Seattle, Washington 98195, USA
    J Biol Chem 280:2413-23. 2005
    ..Together our data suggest a role for bulge nucleotides in enhancing synthesis through stable secondary structures and reducing strand transfer...
  10. pmc Human Tdp1 cleaves a broad spectrum of substrates, including phosphoamide linkages
    Heidrun Interthal
    Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington 98195 7242, USA
    J Biol Chem 280:36518-28. 2005
    ..In combination with earlier data showing that Tdp1 can use 3'-phosphoglycolate as a substrate, these data suggest that Tdp1 may function to remove a variety of 3' adducts from DNA during DNA repair...
  11. pmc Mutational analysis of the preferential binding of human topoisomerase I to supercoiled DNA
    Zheng Yang
    Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195 7242, USA
    FEBS J 276:5906-19. 2009
    ..The results obtained implicate the linker and solvent-exposed basic residues in core subdomain III in the preferential binding of human topoisomerase I to supercoiled DNA...
  12. pmc Assays for the preferential binding of human topoisomerase I to supercoiled DNA
    Zheng Yang
    Department of Microbiology, University of Washington, Seattle, Washington, USA
    Methods Mol Biol 582:49-57. 2009
    ....
  13. ncbi request reprint Single unpaired nucleotides facilitate HIV-1 reverse transcriptase displacement synthesis through duplex RNA
    Christian Lanciault
    Department of Microbiology, University of Washington School of Medicine, Seattle, 98195, USA
    J Biol Chem 279:32252-61. 2004
    ..Introduction of a bulge facilitates displacement synthesis through distal regions by increasing RT processivity in the vicinity of a bulge and reducing the impact of branch migration on primer extension...
  14. ncbi request reprint The role of lysine 532 in the catalytic mechanism of human topoisomerase I
    Heidrun Interthal
    Department of Microbiology, University of Washington School of Medicine, Seattle, Washington 98195 7242, USA
    J Biol Chem 279:2984-92. 2004
    ..The corresponding residues in the vaccinia virus topoisomerase and the tyrosine recombinases may have similar critical roles in catalysis...
  15. ncbi request reprint Insights into substrate binding and catalytic mechanism of human tyrosyl-DNA phosphodiesterase (Tdp1) from vanadate and tungstate-inhibited structures
    Douglas R Davies
    Department of Biochemistry and Biological Structure, University of Washington, Box 357742, Seattle, WA 98195 7242, USA
    J Mol Biol 324:917-32. 2002
    ..These structural models allow predictions to be made regarding the specific binding mode of the substrate and the mechanism of catalysis...
  16. ncbi request reprint Crystal structure of a transition state mimic for Tdp1 assembled from vanadate, DNA, and a topoisomerase I-derived peptide
    Douglas R Davies
    Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
    Chem Biol 10:139-47. 2003
    ....
  17. ncbi request reprint Explorations of peptide and oligonucleotide binding sites of tyrosyl-DNA phosphodiesterase using vanadate complexes
    Douglas R Davies
    Department of Biochemistry, P O Box 357742, School of Medicine, University of Washington, Seattle, Washington 98195 7242, USA
    J Med Chem 47:829-37. 2004
    ....
  18. pmc Preferred sequences within a defined cleavage window specify DNA 3' end-directed cleavages by retroviral RNases H
    Sharon J Schultz
    Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington 98195, USA
    J Biol Chem 284:32225-38. 2009
    ..These data demonstrate that all three modes of retroviral RNase H cleavage share sequence determinants that may be useful in designing assays to identify inhibitors of retroviral RNases H...
  19. ncbi request reprint Reconstitution of enzymatic activity by the association of the cap and catalytic domains of human topoisomerase I
    Zheng Yang
    Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195 7242, USA
    J Biol Chem 277:30815-23. 2002
    ..These results suggest that activation of the catalytic domain of the enzyme for cleavage requires both DNA binding and the presence of the cap region of the protein...
  20. ncbi request reprint The structure of the transition state of the heterodimeric topoisomerase I of Leishmania donovani as a vanadate complex with nicked DNA
    Douglas R Davies
    Department of Biochemistry, Box 357742, University of Washington, Seattle, WA 98195 7742, USA
    J Mol Biol 357:1202-10. 2006
    ..This structure fills a critical gap in the existing ensemble of topoisomerase I structures and provides crucial insights into the catalytic mechanism...
  21. pmc Pausing during reverse transcription increases the rate of retroviral recombination
    Christian Lanciault
    Department of Microbiology, University of Washington, Seattle, 98195 7242, USA
    J Virol 80:2483-94. 2006
    ..Together, these data demonstrate that reverse transcriptase pausing, as observed in vitro, directly correlates with recombination during minus-sense DNA synthesis in vivo...
  22. pmc Sequence, distance, and accessibility are determinants of 5'-end-directed cleavages by retroviral RNases H
    Sharon J Schultz
    Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195, USA
    J Biol Chem 281:1943-55. 2006
    ..Together these finding demonstrate that the selection of 5'-end-directed cleavage sites by retroviral RNases H results from a combination of nucleotide sequence, permissible distance, and accessibility to the RNA 5'-end...
  23. ncbi request reprint Human DNA topoisomerase I: relaxation, roles, and damage control
    John B Leppard
    Department of Microbiology, School of Medicine, University of Washington, P O Box 357242, 1959 N E Pacific St, Seattle, WA 98195 7242, USA
    Chromosoma 114:75-85. 2005
    ..The complexities of the relaxation reaction, the cellular roles, and the pathways that must exist to repair topoisomerase I-mediated DNA damage highlight the importance of continued study of this essential enzyme...
  24. pmc RNase H activity: structure, specificity, and function in reverse transcription
    Sharon J Schultz
    Department of Microbiology, School of Medicine, Box 357242, University of Washington, Seattle, WA 98195, USA
    Virus Res 134:86-103. 2008
    ..Finally, the RNase H activity of HIV-1 is considered as a target for anti-virals as well as a participant in drug resistance...
  25. pmc Specific cleavages by RNase H facilitate initiation of plus-strand RNA synthesis by Moloney murine leukemia virus
    Sharon J Schultz
    Department of Microbiology, School of Medicine, University of Washington, Seattle 98195 7242, USA
    J Virol 77:5275-85. 2003
    ..These data suggest a model in which efficient initiation of plus-strand synthesis requires the generation of a gap immediately following the plus-strand primer 3' terminus...
  26. ncbi request reprint Recognition of internal cleavage sites by retroviral RNases H
    Sharon J Schultz
    Department of Microbiology, Box 357242, School of Medicine, University of Washington, Seattle, WA 98195 7242, USA
    J Mol Biol 344:635-52. 2004
    ..These data reveal that general degradation of the retroviral genome after minus-strand synthesis can occur through sequence-specific cleavages...
  27. pmc Multiple nucleotide preferences determine cleavage-site recognition by the HIV-1 and M-MuLV RNases H
    Sharon J Schultz
    Department of Microbiology, School of Medicine, Box 357242, University of Washington, Seattle, WA 98195, USA
    J Mol Biol 397:161-78. 2010
    ..The sequence preferences of retroviral RNase H likely reflect structural features in the substrate that favor cleavage and represent a novel specificity determinant to consider in drug design...
  28. pmc Arylstibonic acids: novel inhibitors and activators of human topoisomerase IB
    Hyeongnam Kim
    Department of Pharmacology and Molecular Sciences, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205 2185, USA
    Bioorg Chem 36:190-7. 2008
    ..Arylstibonic acid competitive inhibitors may become useful small molecules for elucidating the cellular functions of hTopo...
  29. pmc The cap region of topoisomerase I binds to sites near both ends of simian virus 40 T antigen
    Rupa Roy
    Department of Biological Sciences, University of Delaware, Newark, DE 19716 2590, USA
    J Virol 77:9809-16. 2003
    ....

Research Grants34

  1. PLUS-STRAND PRIMING AND INTEGRATION BY M-MULV & HIV
    JAMES CHAMPOUX; Fiscal Year: 1993
    ..Special DNA substrates will be designed to biochemically separate the two steps of the reaction with the aim of determining the mechanism of the reaction and the role of the IN protein...
  2. DNA BINDING BY HUMAN TOPOISOMERASE I
    JAMES CHAMPOUX; Fiscal Year: 2003
    ..abstract_text> ..
  3. ENZYMOLOGY OF M MULV AND HIV REPLICATION
    JAMES CHAMPOUX; Fiscal Year: 2004
    ..The energetics of the displacement process will be studied by a novel technique that relies on the measurement of positive supercoils generated during displacement synthesis. ..
  4. EUKARYOTIC TOPOISOMERASE I
    JAMES CHAMPOUX; Fiscal Year: 2005
    ..Information gained on the structure and function of Tdp1 may lead to the development of inhibitors of Tdp1 that could be used in combination anticancer drug therapy regimens with camptothecin. ..
  5. The Enzymology of M-MuLV and HIV Replication
    JAMES CHAMPOUX; Fiscal Year: 2007
    ..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. ..
  6. EUKARYOTIC TOPOISOMERASE I
    JAMES CHAMPOUX; Fiscal Year: 2007
    ....
  7. 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. ..
  8. EUKARYOTIC TOPOISOMERASE I
    JAMES CHAMPOUX; Fiscal Year: 2001
    ....
  9. EUKARYOTIC TOPOISOMERASE I
    James J Champoux; Fiscal Year: 2010
    ....