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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 詹迺立 | zh_TW |
| dc.contributor.advisor | Nei-Li Chan | en |
| dc.contributor.author | 陳星甫 | zh_TW |
| dc.contributor.author | Shin-Fu Chen | en |
| dc.date.accessioned | 2021-07-11T15:47:36Z | - |
| dc.date.available | 2024-02-28 | - |
| dc.date.copyright | 2018-10-09 | - |
| dc.date.issued | 2018 | - |
| dc.date.submitted | 2002-01-01 | - |
| dc.identifier.citation | 1. Ju, B. G. et al. A topoisomerase IIbeta-mediated dsDNA break required for regulated transcription. Science 312, 1798-1802 (2006).
2. Vos, S. M., Tretter, E. M., Schmidt, B. H. & Berger, J. M. All tangled up: how cells direct, manage and exploit topoisomerase function. Nat. Rev. Mol. Cell Biol. 12, 827-841 (2011). 3. Liu, L. F. & Wang, J. C. Supercoiling of the DNA template during transcription. Proc. Natl. Acad. Sci. U. S. A. 84, 7024-7027 (1987). 4. Wang, J. C. Cellular roles of DNA topoisomerases: a molecular perspective. Nat. Rev. Mol. Cell Biol. 3, 430-440 (2002). 5. Forterre, P. & Gadelle, D. Phylogenomics of DNA topoisomerases: their origin and putative roles in the emergence of modern organisms. Nucleic Acids Res. 37, 679-692 (2009). 6. Gadelle, D., Filee, J., Buhler, C. & Forterre, P. Phylogenomics of type II DNA topoisomerases. Bioessays 25, 232-242 (2003). 7. Wang, J. C. Interaction between DNA and an Escherichia coli protein omega. Journal of molecular biology 55, 523-533 (1971). 8. Wilson, T. M., Chen, A. D. & Hsieh, T. Cloning and characterization of Drosophila topoisomerase IIIbeta. Relaxation of hypernegatively supercoiled DNA. J. Biol. Chem. 275, 1533-1540 (2000). 9. Plank, J. L., Chu, S. H., Pohlhaus, J. R., Wilson-Sali, T. & Hsieh, T. S. Drosophila melanogaster topoisomerase IIIalpha preferentially relaxes a positively or negatively supercoiled bubble substrate and is essential during development. J. Biol. Chem. 280, 3564-3573 (2005). 10. Dynan, W. S., Jendrisak, J. J., Hager, D. A. & Burgess, R. R. Purification and characterization of wheat germ DNA topoisomerase I (nicking-closing enzyme). J. Biol. Chem. 256, 5860-5865 (1981). 11. Tse-Dinh, Y. C. Uncoupling of the DNA breaking and rejoining steps of Escherichia coli type I DNA topoisomerase. Demonstration of an active covalent protein-DNA complex. J. Biol. Chem. 261, 10931-10935 (1986). 12. Brown, P. O. & Cozzarelli, N. R. Catenation and knotting of duplex DNA by type 1 topoisomerases: a mechanistic parallel with type 2 topoisomerases. Proc. Natl. Acad. Sci. U. S. A. 78, 843-847 (1981). 13. Hiasa, H., DiGate, R. J. & Marians, K. J. Decatenating activity of Escherichia coli DNA gyrase and topoisomerases I and III during oriC and pBR322 DNA replication in vitro. J. Biol. Chem. 269, 2093-2099 (1994). 14. Kim, R. A. & Wang, J. C. Identification of the yeast TOP3 gene product as a single strand-specific DNA topoisomerase. J. Biol. Chem. 267, 17178-17185 (1992). 15. Harmon, F. G., Brockman, J. P. & Kowalczykowski, S. C. RecQ helicase stimulates both DNA catenation and changes in DNA topology by topoisomerase III. J. Biol. Chem. 278, 42668-42678 (2003). 16. DiGate, R. J. & Marians, K. J. Identification of a potent decatenating enzyme from Escherichia coli. J. Biol. Chem. 263, 13366-13373 (1988). 17. Lopez, C. R. et al. A role for topoisomerase III in a recombination pathway alternative to RuvABC. Molecular microbiology 58, 80-101 (2005). 18. Wu, L. & Hickson, I. D. The Bloom's syndrome helicase suppresses crossing over during homologous recombination. Nature 426, 870-874 (2003). 19. Plank, J. L., Wu, J. & Hsieh, T. S. Topoisomerase IIIalpha and Bloom's helicase can resolve a mobile double Holliday junction substrate through convergent branch migration. Proc. Natl. Acad. Sci. U. S. A. 103, 11118-11123 (2006). 20. Kikuchi, A. & Asai, K. Reverse gyrase--a topoisomerase which introduces positive superhelical turns into DNA. Nature 309, 677-681 (1984). 21. Hsieh, T. S. & Plank, J. L. Reverse gyrase functions as a DNA renaturase: annealing of complementary single-stranded circles and positive supercoiling of a bubble substrate. J. Biol. Chem. 281, 5640-5647 (2006). 22. Koster, D. A., Croquette, V., Dekker, C., Shuman, S. & Dekker, N. H. Friction and torque govern the relaxation of DNA supercoils by eukaryotic topoisomerase IB. Nature 434, 671-674 (2005). 23. Laco, G. S. et al. Human topoisomerase I inhibition: docking camptothecin and derivatives into a structure-based active site model. Biochemistry 41, 1428-1435 (2002). 24. Suski, C. & Marians, K. J. Resolution of converging replication forks by RecQ and topoisomerase III. Mol. Cell 30, 779-789 (2008). 25. Forterre, P. DNA topoisomerase V: a new fold of mysterious origin. Trends in biotechnology 24, 245-247 (2006). 26. Taneja, B., Schnurr, B., Slesarev, A., Marko, J. F. & Mondragon, A. Topoisomerase V relaxes supercoiled DNA by a constrained swiveling mechanism. Proc. Natl. Acad. Sci. U. S. A. 104, 14670-14675 (2007). 27. Slesarev, A. I. et al. DNA topoisomerase V is a relative of eukaryotic topoisomerase I from a hyperthermophilic prokaryote. Nature 364, 735-737 (1993). 28. Gellert, M., Mizuuchi, K., O'Dea, M. H. & Nash, H. A. DNA gyrase: an enzyme that introduces superhelical turns into DNA. Proc. Natl. Acad. Sci. U. S. A. 73, 3872-3876 (1976). 29. Bergerat, A., Gadelle, D. & Forterre, P. Purification of a DNA topoisomerase II from the hyperthermophilic archaeon Sulfolobus shibatae. A thermostable enzyme with both bacterial and eucaryal features. J. Biol. Chem. 269, 27663-27669 (1994). 30. Brown, P. O. & Cozzarelli, N. R. A sign inversion mechanism for enzymatic supercoiling of DNA. Science 206, 1081-1083 (1979). 31. Mizuuchi, K., Fisher, L. M., O'Dea, M. H. & Gellert, M. DNA gyrase action involves the introduction of transient double-strand breaks into DNA. Proc. Natl. Acad. Sci. U. S. A. 77, 1847-1851 (1980). 32. Liu, L. F., Rowe, T. C., Yang, L., Tewey, K. M. & Chen, G. L. Cleavage of DNA by mammalian DNA topoisomerase II. J. Biol. Chem. 258, 15365-15370 (1983). 33. Sander, M. & Hsieh, T. Double strand DNA cleavage by type II DNA topoisomerase from Drosophila melanogaster. J. Biol. Chem. 258, 8421-8428 (1983). 34. Lindsley, J. E. & Wang, J. C. Proteolysis patterns of epitopically labeled yeast DNA topoisomerase II suggest an allosteric transition in the enzyme induced by ATP binding. Proc. Natl. Acad. Sci. U. S. A. 88, 10485-10489 (1991). 35. Goto, T. & Wang, J. C. Yeast DNA topoisomerase II. An ATP-dependent type II topoisomerase that catalyzes the catenation, decatenation, unknotting, and relaxation of double-stranded DNA rings. J. Biol. Chem. 257, 5866-5872 (1982). 36. Hsieh, T. & Brutlag, D. ATP-dependent DNA topoisonmerase from D. melanogaster reversibly catenates duplex DNA rings. Cell 21, 115-125 (1980). 37. Forterre, P., Gribaldo, S., Gadelle, D. & Serre, M. C. Origin and evolution of DNA topoisomerases. Biochimie 89, 427-446 (2007). 38. Schoeffler, A. J. & Berger, J. M. DNA topoisomerases: harnessing and constraining energy to govern chromosome topology. Q. Rev. Biophys. 41, 41-101 (2008). 39. Zechiedrich, E. L. et al. Roles of topoisomerases in maintaining steady-state DNA supercoiling in Escherichia coli. J. Biol. Chem. 275, 8103-8113 (2000). 40. Levine, C., Hiasa, H. & Marians, K. J. DNA gyrase and topoisomerase IV: biochemical activities, physiological roles during chromosome replication, and drug sensitivities. Biochim. Biophys. Acta 1400, 29-43 (1998). 41. Peng, H. & Marians, K. J. Decatenation activity of topoisomerase IV during oriC and pBR322 DNA replication in vitro. Proc. Natl. Acad. Sci. U. S. A. 90, 8571-8575 (1993). 42. Zechiedrich, E. L. & Cozzarelli, N. R. Roles of topoisomerase IV and DNA gyrase in DNA unlinking during replication in Escherichia coli. Genes Dev. 9, 2859-2869 (1995). 43. Jenkins, J. R. et al. Isolation of cDNA clones encoding the beta isozyme of human DNA topoisomerase II and localisation of the gene to chromosome 3p24. Nucleic Acids Res. 20, 5587-5592 (1992). 44. Tsai-Pflugfelder, M. et al. Cloning and sequencing of cDNA encoding human DNA topoisomerase II and localization of the gene to chromosome region 17q21-22. Proc. Natl. Acad. Sci. U. S. A. 85, 7177-7181 (1988). 45. Linka, R. M. et al. C-terminal regions of topoisomerase IIalpha and IIbeta determine isoform-specific functioning of the enzymes in vivo. Nucleic Acids Res. 35, 3810-3822 (2007). 46. Bergerat, A. et al. An atypical topoisomerase II from Archaea with implications for meiotic recombination. Nature 386, 414-417 (1997). 47. Malik, S. B., Ramesh, M. A., Hulstrand, A. M. & Logsdon, J. M., Jr. Protist homologs of the meiotic Spo11 gene and topoisomerase VI reveal an evolutionary history of gene duplication and lineage-specific loss. Molecular biology and evolution 24, 2827-2841 (2007). 48. Buhler, C., Lebbink, J. H., Bocs, C., Ladenstein, R. & Forterre, P. DNA topoisomerase VI generates ATP-dependent double-strand breaks with two-nucleotide overhangs. J. Biol. Chem. 276, 37215-37222 (2001). 49. Corbett, K. D. & Berger, J. M. Structure of the topoisomerase VI-B subunit: implications for type II topoisomerase mechanism and evolution. EMBO J. 22, 151-163 (2003). 50. Nichols, M. D., DeAngelis, K., Keck, J. L. & Berger, J. M. Structure and function of an archaeal topoisomerase VI subunit with homology to the meiotic recombination factor Spo11. EMBO J. 18, 6177-6188 (1999). 51. Grue, P. et al. Essential mitotic functions of DNA topoisomerase IIalpha are not adopted by topoisomerase IIbeta in human H69 cells. J. Biol. Chem. 273, 33660-33666 (1998). 52. Carpenter, A. J. & Porter, A. C. Construction, characterization, and complementation of a conditional-lethal DNA topoisomerase IIalpha mutant human cell line. Mol. Biol. Cell 15, 5700-5711 (2004). 53. Laponogov, I. et al. Structure of an 'open' clamp type II topoisomerase-DNA complex provides a mechanism for DNA capture and transport. Nucleic Acids Res. 41, 9911-9923 (2013). 54. Schmidt, B. H., Osheroff, N. & Berger, J. M. Structure of a topoisomerase II-DNA-nucleotide complex reveals a new control mechanism for ATPase activity. Nat. Struct. Mol. Biol. 19, 1147-1154 (2012). 55. Wigley, D. B., Davies, G. J., Dodson, E. J., Maxwell, A. & Dodson, G. Crystal structure of an N-terminal fragment of the DNA gyrase B protein. Nature 351, 624-629 (1991). 56. Berger, J. M., Gamblin, S. J., Harrison, S. C. & Wang, J. C. Structure and mechanism of DNA topoisomerase II. Nature 379, 225-232 (1996). 57. Morais Cabral, J. H. et al. Crystal structure of the breakage-reunion domain of DNA gyrase. Nature 388, 903-906 (1997). 58. Classen, S., Olland, S. & Berger, J. M. Structure of the topoisomerase II ATPase region and its mechanism of inhibition by the chemotherapeutic agent ICRF-187. Proc. Natl. Acad. Sci. U. S. A. 100, 10629-10634 (2003). 59. Dong, K. C. & Berger, J. M. Structural basis for gate-DNA recognition and bending by type IIA topoisomerases. Nature 450, 1201-1205 (2007). 60. Wei, H., Ruthenburg, A. J., Bechis, S. K. & Verdine, G. L. Nucleotide-dependent domain movement in the ATPase domain of a human type IIA DNA topoisomerase. J. Biol. Chem. 280, 37041-37047 (2005). 61. Aravind, L., Leipe, D. D. & Koonin, E. V. Toprim--a conserved catalytic domain in type IA and II topoisomerases, DnaG-type primases, OLD family nucleases and RecR proteins. Nucleic Acids Res. 26, 4205-4213 (1998). 62. Wang, J. C. Moving one DNA double helix through another by a type II DNA topoisomerase: the story of a simple molecular machine. Q. Rev. Biophys. 31, 107-144 (1998). 63. Roca, J. & Wang, J. C. The capture of a DNA double helix by an ATP-dependent protein clamp: a key step in DNA transport by type II DNA topoisomerases. Cell 71, 833-840 (1992). 64. Wyckoff, E., Natalie, D., Nolan, J. M., Lee, M. & Hsieh, T. Structure of the Drosophila DNA topoisomerase II gene. Nucleotide sequence and homology among topoisomerases II. J. Mol. Biol. 205, 1-13 (1989). 65. Austin, C. A., Sng, J. H., Patel, S. & Fisher, L. M. Novel HeLa topoisomerase II is the II beta isoform: complete coding sequence and homology with other type II topoisomerases. Biochimica et biophysica acta 1172, 283-291 (1993). 66. Crenshaw, D. G. & Hsieh, T. Function of the hydrophilic carboxyl terminus of type II DNA topoisomerase from Drosophila melanogaster. II. In vivo studies. J. Biol. Chem. 268, 21335-21343 (1993). 67. Corbett, K. D., Shultzaberger, R. K. & Berger, J. M. The C-terminal domain of DNA gyrase A adopts a DNA-bending beta-pinwheel fold. Proc. Natl. Acad. Sci. U. S. A. 101, 7293-7298 (2004). 68. Hsieh, T. J., Farh, L., Huang, W. M. & Chan, N. L. Structure of the topoisomerase IV C-terminal domain: a broken beta-propeller implies a role as geometry facilitator in catalysis. J. Biol. Chem. 279, 55587-55593 (2004). 69. Corbett, K. D., Schoeffler, A. J., Thomsen, N. D. & Berger, J. M. The structural basis for substrate specificity in DNA topoisomerase IV. J. Mol. Biol. 351, 545-561 (2005). 70. McClendon, A. K. et al. Bimodal recognition of DNA geometry by human topoisomerase II alpha: preferential relaxation of positively supercoiled DNA requires elements in the C-terminal domain. Biochemistry 47, 13169-13178 (2008). 71. Jensen, S. et al. Analysis of functional domain organization in DNA topoisomerase II from humans and Saccharomyces cerevisiae. Mol. Cell. Biol. 16, 3866-3877 (1996). 72. Caron, P. R., Watt, P. & Wang, J. C. The C-terminal domain of Saccharomyces cerevisiae DNA topoisomerase II. Mol. Cell. Biol. 14, 3197-3207 (1994). 73. Kampranis, S. C. & Maxwell, A. Conversion of DNA gyrase into a conventional type II topoisomerase. Proc. Natl. Acad. Sci. U. S. A. 93, 14416-14421 (1996). 74. Ruthenburg, A. J., Graybosch, D. M., Huetsch, J. C. & Verdine, G. L. A superhelical spiral in the Escherichia coli DNA gyrase A C-terminal domain imparts unidirectional supercoiling bias. J. Biol. Chem. 280, 26177-26184 (2005). 75. Roca, J., Berger, J. M., Harrison, S. C. & Wang, J. C. DNA transport by a type II topoisomerase: direct evidence for a two-gate mechanism. Proc. Natl. Acad. Sci. U. S. A. 93, 4057-4062 (1996). 76. Bax, B. D. et al. Type IIA topoisomerase inhibition by a new class of antibacterial agents. Nature 466, 935-940 (2010). 77. Schmidt, B. H., Burgin, A. B., Deweese, J. E., Osheroff, N. & Berger, J. M. A novel and unified two-metal mechanism for DNA cleavage by type II and IA topoisomerases. Nature 465, 641-644 (2010). 78. Laponogov, I. et al. Structural insight into the quinolone-DNA cleavage complex of type IIA topoisomerases. Nat. Struct. Mol. Biol. 16, 667-669 (2009). 79. Laponogov, I. et al. Structural basis of gate-DNA breakage and resealing by type II topoisomerases. PLoS One 5, e11338 (2010). 80. Wu, C. C. et al. Structural basis of type II topoisomerase inhibition by the anticancer drug etoposide. Science 333, 459-462 (2011). 81. Pommier, Y., Leo, E., Zhang, H. & Marchand, C. DNA topoisomerases and their poisoning by anticancer and antibacterial drugs. Chem. Biol. 17, 421-433 (2010). 82. Pommier, Y. Drugging Topoisomerases: Lessons and Challenges. ACS Chemical Biology 8, 82-95 (2013). 83. Wasserman, R. A. & Wang, J. C. Analysis of yeast DNA topoisomerase II mutants resistant to the antitumor drug amsacrine. Cancer research 54, 1795-1800 (1994). 84. Hooper, D. C. & Jacoby, G. A. Topoisomerase Inhibitors: Fluoroquinolone Mechanisms of Action and Resistance. Cold Spring Harb Perspect Med 6 (2016). 85. Otwinowski, Z. & Minor, W. Processing of X-ray diffraction data collected in oscillation mode. Macromolecular Crystallography, Pt A 276, 307-326 (1997). 86. Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta. Crystallogr. D Biol. Crystallogr. 66, 213-221 (2010). 87. Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta crystallographica. Section D, Biological crystallography 66, 486-501 (2010). 88. Schrodinger, LLC (2010). 89. Huang, N. L. & Lin, J. H. Recovery of the poisoned topoisomerase II for DNA religation: coordinated motion of the cleavage core revealed with the microsecond atomistic simulation. Nucleic Acids Res. 43, 6772-6786 (2015). 90. Dolinsky, T. J., Nielsen, J. E., McCammon, J. A. & Baker, N. A. PDB2PQR: an automated pipeline for the setup of Poisson-Boltzmann electrostatics calculations. Nucleic Acids Res. 32, W665-667 (2004). 91. Dolinsky, T. J. et al. PDB2PQR: expanding and upgrading automated preparation of biomolecular structures for molecular simulations. Nucleic Acids Res. 35, W522-525 (2007). 92. Palermo, G., Stenta, M., Cavalli, A., Dal Peraro, M. & De Vivo, M. Molecular Simulations Highlight the Role of Metals in Catalysis and Inhibition of Type II Topoisomerase. Journal of chemical theory and computation 9, 857-862 (2013). 93. Case, D. A. et al. The Amber biomolecular simulation programs. J. Comput. Chem. 26, 1668-1688 (2005). 94. Salomon-Ferrer, R., Case, D. A. & Walker, R. C. An overview of the Amber biomolecular simulation package. Wires Comput. Mol. Sci. 3, 198-210 (2013). 95. Warshel, A., Papazyan, A. & Kollman, P. A. On low-barrier hydrogen bonds and enzyme catalysis. Science 269, 102-106 (1995). 96. Duan, Y. et al. A point-charge force field for molecular mechanics simulations of proteins based on condensed-phase quantum mechanical calculations. J. Comput. Chem. 24, 1999-2012 (2003). 97. Perez, A. et al. Refinenement of the AMBER force field for nucleic acids: Improving the description of alpha/gamma conformers. Biophys. J 92, 3817-3829 (2007). 98. Jorgensen, W. L., Chandrasekhar, J., Madura, J. D., Impey, R. W. & Klein, M. L. Comparison of simple potential functions for simulating liquid water. J. Chemical Phys. 79, 926-935 (1983). 99. Izrailev, S., Stepaniants, S., Balsera, M., Oono, Y. & Schulten, K. Molecular dynamics study of unbinding of the avidin-biotin complex. Biophys. J. 72, 1568-1581 (1997). 100. Isralewitz, B., Gao, M. & Schulten, K. Steered molecular dynamics and mechanical functions of proteins. Curr. Opin. Struct. Biol. 11, 224-230 (2001). 101. Hopkins, C. W., Le Grand, S., Walker, R. C. & Roitberg, A. E. Long-Time-Step Molecular Dynamics through Hydrogen Mass Repartitioning. J. Chem. Theory Comput 11, 1864-1874 (2015). 102. Ryckaert, J.-P. C., G.; Berendsen, H.J.C. Numerical integration of the cartesian equations of motion of a system with constraints: Molecular dynamics of n-alkanes. J. Comput. Phys. 23, 327–341 (1977). 103. Roe, D. R. & Cheatham, T. E., 3rd PTRAJ and CPPTRAJ: Software for Processing and Analysis of Molecular Dynamics Trajectory Data. J. Chem. Theory. Comput. 9, 3084-3095 (2013). 104. Kondrashov, D. A., Zhang, W., Aranda, R. t., Stec, B. & Phillips, G. N., Jr. Sampling of the native conformational ensemble of myoglobin via structures in different crystalline environments. Proteins 70, 353-362 (2008). 105. Motlagh, H. N., Wrabl, J. O., Li, J. & Hilser, V. J. The ensemble nature of allostery. Nature 508, 331-339 (2014). 106. Wohlkonig, A. et al. Structural basis of quinolone inhibition of type IIA topoisomerases and target-mediated resistance. Nat. Struct. Mol. Biol. 17, 1152-1153 (2010). 107. Wang, Y. R. et al. Producing irreversible topoisomerase II-mediated DNA breaks by site-specific Pt(II)-methionine coordination chemistry. Nucleic acids research 45, 10861-10871 (2017). 108. Wu, C. C., Li, Y. C., Wang, Y. R., Li, T. K. & Chan, N. L. On the structural basis and design guidelines for type II topoisomerase-targeting anticancer drugs. Nucleic Acids Res. 41, 10630-10640 (2013). 109. Fass, D., Bogden, C. E. & Berger, J. M. Quaternary changes in topoisomerase II may direct orthogonal movement of two DNA strands. Nat. Struct. Biol. 6, 322-326 (1999). 110. Hartman Chen, S., Chan, N. L. & Hsieh, T. S. New Mechanistic and Functional Insights into DNA Topoisomerases. Annu. Rev. Biochem. (2013). 111. Stone, M. D. et al. Chirality sensing by Escherichia coli topoisomerase IV and the mechanism of type II topoisomerases. Proc. Natl. Acad. Sci. U. S. A. 100, 8654-8659 (2003). 112. Crisona, N. J., Strick, T. R., Bensimon, D., Croquette, V. & Cozzarelli, N. R. Preferential relaxation of positively supercoiled DNA by E. coli topoisomerase IV in single-molecule and ensemble measurements. Genes Dev. 14, 2881-2892 (2000). 113. McClendon, A. K., Rodriguez, A. C. & Osheroff, N. Human topoisomerase IIalpha rapidly relaxes positively supercoiled DNA: implications for enzyme action ahead of replication forks. J. Biol. Chem. 280, 39337-39345 (2005). 114. Fernandez, X., Diaz-Ingelmo, O., Martinez-Garcia, B. & Roca, J. Chromatin regulates DNA torsional energy via topoisomerase II-mediated relaxation of positive supercoils. EMBO J. 33, 1492-1501 (2014). 115. Timsit, Y. Local sensing of global DNA topology: from crossover geometry to type II topoisomerase processivity. Nucleic acids research 39, 8665-8676 (2011). 116. Rudolph, M. G. & Klostermeier, D. Mapping the spectrum of conformational states of the DNA- and C-gates in Bacillus subtilis gyrase. J. Mol. Biol. 425, 2632-2640 (2013). 117. Du, D., van Veen, H. W., Murakami, S., Pos, K. M. & Luisi, B. F. Structure, mechanism and cooperation of bacterial multidrug transporters. Curr. Opin. Struct. Biol. 33, 76-91 (2015). 118. Ryan, R. M. & Vandenberg, R. J. Elevating the alternating-access model. Nat. Struct. Mol. Biol. 23, 187-189 (2016). 119. Locher, K. P. Mechanistic diversity in ATP-binding cassette (ABC) transporters. Nat. Struct. Mol. Biol. 23, 487-493 (2016). 120. Peng, H. & Marians, K. J. Escherichia coli topoisomerase IV. Purification, characterization, subunit structure, and subunit interactions. J. Biol. Chem. 268, 24481-24490 (1993). 121. Baker, N. M., Weigand, S., Maar-Mathias, S. & Mondragon, A. Solution structures of DNA-bound gyrase. Nucleic Acids Res. 39, 755-766 (2011). 122. Papillon, J. et al. Structural insight into negative DNA supercoiling by DNA gyrase, a bacterial type 2A DNA topoisomerase. Nucleic Acids Res. 41, 7815-7827 (2013). 123. Smiley, R. D., Collins, T. R., Hammes, G. G. & Hsieh, T. S. Single-molecule measurements of the opening and closing of the DNA gate by eukaryotic topoisomerase II. Proc. Natl. Acad. Sci. U. S. A. 104, 4840-4845 (2007). 124. Huang, W. C., Lee, C. Y. & Hsieh, T. S. Single-molecule Forster resonance energy transfer (FRET) analysis discloses the dynamics of the DNA-topoisomerase II (Top2) interaction in the presence of TOP2-targeting agents. J. Biol. Chem. 292, 12589-12598 (2017). 125. Gubaev, A., Hilbert, M. & Klostermeier, D. The DNA-gate of Bacillus subtilis gyrase is predominantly in the closed conformation during the DNA supercoiling reaction. Proc. Natl. Acad. Sci. U. S. A. 106, 13278-13283 (2009). 126. Palermo, G. et al. An optimized polyamine moiety boosts the potency of human type II topoisomerase poisons as quantified by comparative analysis centered on the clinical candidate F14512. Chemical communications (Cambridge, England) 51, 14310-14313 (2015). 127. Neyer, S. et al. Structure of RNA polymerase I transcribing ribosomal DNA genes. Nature (2016). 128. Deweese, J. E. & Osheroff, N. The DNA cleavage reaction of topoisomerase II: wolf in sheep's clothing. Nucleic Acids Res. 37, 738-748 (2009). 129. Bates, A. D., Berger, J. M. & Maxwell, A. The ancestral role of ATP hydrolysis in type II topoisomerases: prevention of DNA double-strand breaks. Nucleic Acids Res. 39, 6327-6339 (2011). 130. Wendorff, T. J., Schmidt, B. H., Heslop, P., Austin, C. A. & Berger, J. M. The structure of DNA-bound human topoisomerase II alpha: conformational mechanisms for coordinating inter-subunit interactions with DNA cleavage. J. Mol. Biol. 424, 109-124 (2012). 131. Germe, T. et al. A new class of antibacterials, the imidazopyrazinones, reveal structural transitions involved in DNA gyrase poisoning and mechanisms of resistance. Nucleic acids research 46, 4325 (2018). 132. Heddle, J. G. et al. The antibiotic microcin B17 is a DNA gyrase poison: characterisation of the mode of inhibition. J. Mol. Biol. 307, 1223-1234 (2001). 133. Collin, F., Karkare, S. & Maxwell, A. Exploiting bacterial DNA gyrase as a drug target: current state and perspectives. Appl. Microbiol. Biotechnol. 92, 479-497 (2011). 134. Parks, W. M., Bottrill, A. R., Pierrat, O. A., Durrant, M. C. & Maxwell, A. The action of the bacterial toxin, microcin B17, on DNA gyrase. Biochimie 89, 500-507 (2007). 135. Dao-Thi, M. H. et al. Molecular basis of gyrase poisoning by the addiction toxin CcdB. J. Mol. Biol. 348, 1091-1102 (2005). 136. Smith, A. B. & Maxwell, A. A strand-passage conformation of DNA gyrase is required to allow the bacterial toxin, CcdB, to access its binding site. Nucleic Acids Res. 34, 4667-4676 (2006). | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/79144 | - |
| dc.description.abstract | 第二型拓樸異構酶(Top2)是一類普遍存在於古生菌、細菌及真核生物中的重要蛋白。Top2可以利用ATP分子之結合與水解所帶動的蛋白構型變化來改變兩條雙股DNA的交會方式(handedness of DNA crossovers)。透過其獨特的酵素活性，Top2可以操控DNA拓樸構型並移除細胞中可能阻礙DNA運作的結構(包括超螺旋、扭結或套鎖)，使DNA代謝作用得以順利進行。在作用機制上，這類具有二維對稱構型的酵素首先會與一條稱為G-segment的雙股DNA結合，接著兩個具備催化轉酯反應能力的酵素活性中心會以酪胺酸作為親核基攻擊G-segment DNA磷酸雙酯骨架，並與5′端的磷酸根形成共價的磷酸酪胺基鍵(phosphotyrosyl bond)，造成暫時性的DNA雙股斷裂。再透過ATP分子結合與水解所誘發的酵素四級構型變化促使另一條被稱為T-segment的雙股DNA通過由蛋白與G-segment共同形成的閘門(DNA-gate)以達成DNA拓樸構型的改變。然而，儘管DNA-gate的形成及開闔方式對於Top2是否可以順利完成其DNA搬運的功能扮演極為重要的關鍵角色，過去對此區域的結構研究僅侷限於關閉構型。
在本論文中，我們利用了X-射線晶體學成功解析了第一個以開啟狀態呈現的DNA-gate結構。透過對此新構型的分析，我們闡明了過去因為缺乏相關結構資訊而尚未解決的問題，包括: Top2 是如何開啟其DNA-gate區域? 與酵素共價連接的DNA ends在DNA-gate開啟後會產生何種構型變化? 以及預期會讓T-segment穿越的通道(T-segment conducting channel) 在DNA-gate開啟後會呈現出什麼樣的結構特性? 除了這些議題，我們也從T-segment conducting channel的走向了解到第二型拓樸異構酶為何對於正超螺旋DNA有較好的催化效果。由於此構型係對應至T-segment穿越缺口的早期型態，我們團隊也透過電腦的計算，成功模擬出Top2可能會以類似ABC transproter運輸小分子的形變方式(rocker-switch-type movement)協助T-segment DNA穿越DNA-gate。鑒於Top2是臨床許多抗生素與抗癌小分子的標靶，我們認為此新構型可以做為發展新式Top2標的藥物的平台，有機會解決目前難以克服關於抗藥性的問題。另一方面，除了針對DNA-gate 開闔所衍伸出的議題進行探討外，本研究亦藉由解析人類Top2 DNA-gate片段的原態晶體結構，並透過一系列生化實驗及結構比對分析，提出了第二型拓樸異構酶是如何從其原態構型組裝成具有切割活性的蛋白DNA複合體之模型。 | zh_TW |
| dc.description.abstract | Type II DNA topoisomerases (Top2s) exploit protein conformational changes driven by ATP binding and hydrolysis to direct the passage of one DNA duplex through another, leading to a topological transformation of the DNA. This hallmark DNA passage activity makes Top2s particularly suitable for resolving DNA entanglements arising from cellular DNA transactions, including replication, transcription, chromosome segregation and recombination. To change the topology of DNA, Top2 first introduces a transient double-strand break in a stretch of duplex DNA called the G-segment, which is bound to the enzyme. Another stretch of duplex DNA, called the T-segment, passes through this break and then through the part of the enzyme holding the G-segment, which is called the DNA-gate. The structural basis governing the assembly, opening and closure of the DNA-gate is arguably the most important question to be addressed for a complete mechanistic understanding of Top2 function, as it is this step which allows DNA passage and hence the change in topology. Because directional transport of the T-segment is achieved via coordinated opening and closure of the N-gate, DNA-gate, and C-gate, a full understanding of the catalytic mechanism of Top2 requires structural characterization of these three gates in distinct conformational states. Previous crystallographic studies have revealed the structural details of the N-gate in its open and nucleotide-bound, closed forms. The C-gate has also been resolved in both open and closed conformation. In contrast, whereas multiple crystal structures are available for the closed DNA-gate, opening of the DNA-gate has never been directly visualized. Consequently, outstanding issues regarding the operation of the DNA-gate remain poorly defined, including the architectural and surface features of the T-segment-conducting path, the tertiary and quaternary structural changes associated with gate-opening, and the structural changes of the enzyme-linked DNA cohesive ends upon their detachment from one another. Thus, a step-by-step description of how the T-segment is transported through the DNA-gate is not yet available. In addition, various clinically active anticancer drugs and antibacterials act by targeting the Top2-mediated DNA-gate to produce cytotoxic DNA lesions. Obtaining a more complete picture of the conformational landscape of the DNA-gate will contribute to the development of new Top2-targeting agents.
We report herein the first high-resolution view of the opening of the Top2 DNA-gate, which directly mediates the resolution of topological strand crossings. This new structure not only reveals the formation and structural features of the T-segment-conducting path, but also uncovers unexpected, functionally relevant, conformational changes that accompany the closed-to-open transition. Moreover, using this new structure as the starting point, we further simulated the passage of the T-segment through the DNA-gate by steered molecular dynamics (MD) simulations, providing crucial insights into this central yet elusive step in Top2 catalysis. We have also determined the structures of human Top2α and Top2β DNA-gate in their apo, DNA-free state at 2.67 Å and 2.8 Å, respectively. To our knowledge, these structures provide the first view of eukaryotic DNA-gate in a conformation suitable for engaging in G-segment binding. Structural comparisons between the newly determined apo form and Top2-DNA complex reveal that both prokaryotic and eukaryotic Top2 may undergo a similar G-segment-induced rearrangement of its DNA-binding groove, suggesting an unified mechanism of DNA-gate assembly. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T15:47:36Z (GMT). No. of bitstreams: 1 ntu-107-F98442019-1.pdf: 6886713 bytes, checksum: 48a515d397ab1bed50ba8c1bb8625200 (MD5) Previous issue date: 2018 | en |
| dc.description.tableofcontents | 口試委員審查書 I
謝誌 II 中文摘要 V Abstract VII Abbreviations X Contents XI 1、 Introduction 1 1.1. DNA topoisomerases: essential DNA-manipulating enzymes responsible for resolving intra- and intermolecular DNA entanglements 2 1.2. Classification and Nomenclature of DNA topoisomerases 5 1.2.1. Type IA topoisomerases 5 1.2.2. Type IB topoisomerases 6 1.2.3. Type IC topoisomerases 7 1.2.4. Type IIA topoisomerases 8 1.2.5. Type IIB topoisomerases 10 1.3. Structure and mechanism of Type IIA topoisomerase 10 1.3.1. Overall architecture of Type IIA topoisomerases 11 1.3.2. The DNA strand passage reaction mediated by Type IIA topoisomerases 13 1.4. DNA-gate: the central element in Top2 catalysis 15 Methods and Materials 18 2.1. Construction, expression, and purification of recombinant hTop2αcore and hTop2βcore 19 2.1.1. Preparation of recombinant hTop2αcore 19 2.1.2. Preparation of recombinant hTop2βcore 20 2.2. DNA Substrate for Crystallography 22 2.3. Crystallization 23 2.3.1. Crystallization of the hTop2βcore-DNA cleavage complex (open conformation, iodine-labeled open conformation, and iodine-labeled closed conformation) 23 2.3.2. Crystallization of Apo hTop2αcore 24 2.3.3. Crystallization of Apo hTop2βcore 25 2.4. Data collection and structure determination 26 2.4.1. hTop2core-DNA cleavage complex (open conformation, iodine-labeled open conformation, and iodine-labeled closed conformation) 26 2.4.2. Apo form Top2αcore 27 2.4.3. Apo form Top2βcore 28 2.5. Computational analysis 28 2.5.1. Steered molecular dynamics simulation and structural analysis (This part was performed by Dr. Nan-Lan Huang) 28 2、 Results 32 3.1. Structural Insights into the Gating of DNA Passage by the Topoisomerase II DNA-Gate (This part has been published in Nature communications) 33 3.1.1. A new quaternary conformation of the Top2 cleavage complex reveals opening of the DNA-gate 33 3.1.2. Opening of the DNA-gate involves sliding of two subunits against each other, combined with intra-subunit flexing 37 3.1.3. Structural features of the open DNA-gate 39 3.1.4. Molecular dynamics of T-segment passage through the DNA-gate 41 3.2. Structural Insights into the DNA-gate Assembly mediated by Human Top2 44 3.2.1. Crystal Structures of Apo Human Top2αcore and Top2βcore 44 3.2.2. Structural comparisons reveal that both prokaryotic and eukaryotic Top2s may undergo similar G-segment induced DNA binding groove rearrangement 45 3、 Conclusion and Discussion 47 4、 Figures 61 Figure 1. Structure and mechanism of type IIA topoisomerase (Top2). 62 Figure 2. Crystals of hTop2βcore –DNA cleavage complex. 63 Figure 3. Crystals of apo human Top2core. 64 Figure 4. Diffraction pattern of hTop2βcore-DNA binary complex with partially open DNA-gate. 65 Figure 5. Construction of a functionally relevant Top2 homodimer. The asymmetric unit is composed of one Top2 monomer (gray) bound to a 9-bp DNA duplex (blue). 66 Figure 6. Top2 in open and closed conformation exhibit distinct crystal packing interactions. 67 Figure 7. Diffraction pattern of apo hTop2βcore crystal. 68 Figure 8. A new quaternary conformation of the Top2 cleavage complex showing opening of the DNA-gate. 69 Figure 9. The electron density maps of the bound DNA in the human Top2βcore -DNA binary complex in the partially open conformation. 71 Figure 10. The first three nucleotides of the protein-linked cohesive end become fully disordered upon DNA-gate opening. 72 Figure 11. Both biochemical and crystallographic analysis support the newly determined structure being a bona fide Top2 cleavage complex. 73 Figure 12. Closed-up views of iodine-modified sites in closed or partially open DNA-gate structures. 75 Figure 13. Superimposition of Top2core structures obtained using native and iodine-modified DNA duplex. 76 Figure 14. Based on the integrity of the G-segment, occupancy of the two divalent metal ion binding sites, and the formation of the phosphotyrosyl bond, the structures of the DNA-Top2 complexes can be grouped into six classes that may represent snapshots of Top2 at different catalytic stages during the DNA cleavage reaction. 77 Figure 15. Structural comparison reveals quaternary and tertiary changes associated with DNA-gate opening. 80 Figure 16. Opening of the DNA-gate reveals structural features of the T-segment-conducting path. 82 Figure 17. Surface features of the T-segment-conducting path. 84 Figure 18. A schematic diagram illustrating the strategy used for conducting the steered molecular dynamics simulations. 86 Figure 19. Steered molecular dynamics simulations reveal a common structural snapshot adopted by the hTop2β and the Bacillus gyrase. 88 Figure 20. Five snapshots taken from the steered MD simulation 91 The simulation 91 Figure 21. The Top2-catalyzed DNA passage may be achieved by a “rocker-switch”-type conformational change of the DNA-gate. 93 Figure 22. Crystal structures of the DNA-binding and cleavage core of human Top2s in their apo conformation. 95 Figure 23. The G-segment dependent conformational change observed in A. baumannii topo IV can also be seen in structures of human Top2s. 97 Figure 24. Structural comparison of A. baumannii topo IV (prokaryotic Top2) in the apo and protein-mixofloxacin-DNA complex conformation 98 Figure 25. The ion-pair formed between Toprim and WHD is likely conserved among Top2s. 100 Figure 26. The structural alignment of five selected intermediate structures 101 Figure 27. The newly observed conformational state of Top2 may be targeted for the production of DNA double-strand breaks. 102 Figure 28. Assembly of the DNA-gate 104 5、 Tables 105 Table 1. Statistics for the highest-resolution shell are shown in parentheses. 107 6、 References 109 7、 Appendix 120 | - |
| dc.language.iso | en | - |
| dc.subject | X-射線晶體學 | zh_TW |
| dc.subject | 第二型拓樸異構? | zh_TW |
| dc.subject | DNA閘門 | zh_TW |
| dc.subject | 晶體結構 | zh_TW |
| dc.subject | 蛋白DNA複合體 | zh_TW |
| dc.subject | crystal structure | en |
| dc.subject | steered molecular dynamics | en |
| dc.subject | Type II DNA topoisomerases | en |
| dc.subject | T-segment-conducting path | en |
| dc.subject | DNA-gate | en |
| dc.title | 藉由結構生物學探討第二型拓樸異構酶其DNA閘門區域之構型變化及其運作之分子機制 | zh_TW |
| dc.title | Structural insights into the assembly, opening and gating of DNA passage through the Topoisomerase II DNA-gate | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 106-2 | - |
| dc.description.degree | 博士 | - |
| dc.contributor.oralexamcommittee | 林敬哲;冀宏源;徐駿森;張崇毅;袁小琀 | zh_TW |
| dc.contributor.oralexamcommittee | Jing-Jer Lin;Hung-Yuan (Peter) Chi;Chun-Hua Hsu;Chung-I Chang;Hanna S. Yuan | en |
| dc.subject.keyword | 第二型拓樸異構?,X-射線晶體學,晶體結構,DNA閘門,蛋白DNA複合體, | zh_TW |
| dc.subject.keyword | Type II DNA topoisomerases,crystal structure,DNA-gate,T-segment-conducting path,steered molecular dynamics, | en |
| dc.relation.page | 123 | - |
| dc.identifier.doi | 10.6342/NTU201802353 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2018-08-02 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 生物化學暨分子生物學研究所 | - |
| dc.date.embargo-lift | 2023-10-09 | - |
| 顯示於系所單位： | 生物化學暨分子生物學科研究所 | |
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