Research Topics
Species | JAMES CHAMPOUXSummaryAffiliation: University of Washington Country: USA Publications
Research Grants
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Detail Information
Publications
Structure-based analysis of the effects of camptothecin on the activities of human topoisomerase IJ 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...- DNA topoisomerases: structure, function, and mechanismJ 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... - A first view of the structure of a type IA topoisomerase with bound DNAJames J Champoux
Dept of Microbiology, Box 357242, School of Medicine, University of Washington, Seattle, WA 98195, USA
Trends Pharmacol Sci 23:199-201. 2002.... 
Type IA DNA topoisomerases: strictly one step at a timeJames 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- Ribonuclease H: properties, substrate specificity and roles in retroviral reverse transcriptionJames J Champoux
Department of Microbiology, University of Washington, Seattle, WA 98195, USA
FEBS J 276:1506-16. 2009.... - The crystal structure of human tyrosyl-DNA phosphodiesterase, Tdp1Douglas 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... - DNA relaxation by human topoisomerase I occurs in the closed clamp conformation of the proteinJames 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... - Requirements for DNA unpairing during displacement synthesis by HIV-1 reverse transcriptaseJamie Winshell
Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195-7242, USA
J Biol Chem 279:52924-33. 2004.... - Effects of unpaired nucleotides within HIV-1 genomic secondary structures on pausing and strand transferChristian 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... - Human Tdp1 cleaves a broad spectrum of substrates, including phosphoamide linkagesHeidrun 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... - Mutational analysis of the preferential binding of human topoisomerase I to supercoiled DNAZheng 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... - Assays for the preferential binding of human topoisomerase I to supercoiled DNAZheng Yang
Department of Microbiology, University of Washington, Seattle, Washington, USA
Methods Mol Biol 582:49-57. 2009.... - Single unpaired nucleotides facilitate HIV-1 reverse transcriptase displacement synthesis through duplex RNAChristian 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... - The role of lysine 532 in the catalytic mechanism of human topoisomerase IHeidrun 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... - Insights into substrate binding and catalytic mechanism of human tyrosyl-DNA phosphodiesterase (Tdp1) from vanadate and tungstate-inhibited structuresDouglas 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... - Crystal structure of a transition state mimic for Tdp1 assembled from vanadate, DNA, and a topoisomerase I-derived peptideDouglas R Davies
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA
Chem Biol 10:139-47. 2003.... - Explorations of peptide and oligonucleotide binding sites of tyrosyl-DNA phosphodiesterase using vanadate complexesDouglas 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.... - Preferred sequences within a defined cleavage window specify DNA 3' end-directed cleavages by retroviral RNases HSharon 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... - Reconstitution of enzymatic activity by the association of the cap and catalytic domains of human topoisomerase IZheng 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... - The structure of the transition state of the heterodimeric topoisomerase I of Leishmania donovani as a vanadate complex with nicked DNADouglas 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... - Pausing during reverse transcription increases the rate of retroviral recombinationChristian 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... - Sequence, distance, and accessibility are determinants of 5'-end-directed cleavages by retroviral RNases HSharon 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... - Human DNA topoisomerase I: relaxation, roles, and damage controlJohn 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... - RNase H activity: structure, specificity, and function in reverse transcriptionSharon 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... - Specific cleavages by RNase H facilitate initiation of plus-strand RNA synthesis by Moloney murine leukemia virusSharon 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... - Recognition of internal cleavage sites by retroviral RNases HSharon 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... - Multiple nucleotide preferences determine cleavage-site recognition by the HIV-1 and M-MuLV RNases HSharon 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... - Arylstibonic acids: novel inhibitors and activators of human topoisomerase IBHyeongnam 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... - The cap region of topoisomerase I binds to sites near both ends of simian virus 40 T antigenRupa Roy
Department of Biological Sciences, University of Delaware, Newark, DE 19716-2590, USA
J Virol 77:9809-16. 2003....
Research Grants
- PLUS-STRAND PRIMING AND INTEGRATION BY M-MULV & HIVJAMES 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...
- DNA BINDING BY HUMAN TOPOISOMERASE IJAMES CHAMPOUX; Fiscal Year: 2003..abstract_text> ..
- ENZYMOLOGY OF M MULV AND HIV REPLICATIONJAMES 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. ..
- EUKARYOTIC TOPOISOMERASE IJAMES 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. ..
- The Enzymology of M-MuLV and HIV ReplicationJAMES 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. ..
- EUKARYOTIC TOPOISOMERASE IJAMES CHAMPOUX; Fiscal Year: 2007....
- The Enzymology of M-MuLV and HIV ReplicationJAMES 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. ..
- EUKARYOTIC TOPOISOMERASE IJAMES CHAMPOUX; Fiscal Year: 2001....
- EUKARYOTIC TOPOISOMERASE IJames J Champoux; Fiscal Year: 2010....