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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 冀宏源(Hung-Yuan Chi) | |
| dc.contributor.author | Guan-Chin Su | en |
| dc.contributor.author | 蘇綸勤 | zh_TW |
| dc.date.accessioned | 2021-06-15T11:19:00Z | - |
| dc.date.available | 2021-08-26 | |
| dc.date.copyright | 2016-08-26 | |
| dc.date.issued | 2016 | |
| dc.date.submitted | 2016-08-18 | |
| dc.identifier.citation | 1. Ciccia, A. and Elledge, S.J. (2010) The DNA Damage Response: Making It Safe
to Play with Knives. Mol Cell, 40, 179-204. 2. Lord, C.J. and Ashworth, A. (2012) The DNA damage response and cancer therapy. Nature, 481, 287-294. 3. Prakash, R., Zhang, Y., Feng, W. and Jasin, M. (2015) Homologous recombination and human health: the roles of BRCA1, BRCA2, and associated proteins. Cold Spring Harb Perspect Biol, 7, a016600. 4. Harper, J.W. and Elledge, S.J. (2007) The DNA damage response: ten years after. Mol Cell, 28, 739-745. 5. Jackson, S.P. and Bartek, J. (2009) The DNA-damage response in human biology and disease. Nature, 461, 1071-1078. 6. Pfeiffer, P., Goedecke, W. and Obe, G. (2000) Mechanisms of DNA double-strand break repair and their potential to induce chromosomal aberrations. Mutagenesis, 15, 289-302. 7. Chapman, J.R., Taylor, M.R. and Boulton, S.J. (2012) Playing the end game: DNA double-strand break repair pathway choice. Mol Cell, 47, 497-510. 8. Lieber, M.R. (2010) The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annu Rev Biochem, 79, 181-211. 9. San Filippo, J., Sung, P. and Klein, H. (2008) Mechanism of eukaryotic homologous recombination. Annu Rev Biochem, 77, 229-257. 10. Bell, J.C. and Kowalczykowski, S.C. (2016) Mechanics and Single-Molecule Interrogation of DNA Recombination. Annu Rev Biochem, 85, 193-226. 11. Kowalczykowski, S.C. (2015) An Overview of the Molecular Mechanisms of Recombinational DNA Repair. Cold Spring Harb Perspect Biol, 7. 12. Bizard, A.H. and Hickson, I.D. (2014) The dissolution of double Holliday junctions. Cold Spring Harb Perspect Biol, 6, a016477. 13. Game, J.C. and Mortimer, R.K. (1974) A genetic study of x-ray sensitive mutants in yeast. Mutat Res, 24, 281-292. 14. Kunz, B.A. and Haynes, R.H. (1981) Phenomenology and genetic control of mitotic recombination in yeast. Annu Rev Genet, 15, 57-89. 15. Resnick, M.A., Westmoreland, J., Amaya, E. and Bloom, K. (1987) UV-induced damage and repair in centromere DNA of yeast. Mol Gen Genet, 210, 16-22. 16. Bell, J.C. and Kowalczykowski, S.C. (2016) RecA: Regulation and Mechanism of a Molecular Search Engine. Trends Biochem Sci, 41, 491-507. 17. Sung, P. and Klein, H. (2006) Mechanism of homologous recombination: mediators and helicases take on regulatory functions. Nat Rev Mol Cell Biol, 7, 739-750. 18. Yu, X., Jacobs, S.A., West, S.C., Ogawa, T. and Egelman, E.H. (2001) Domain structure and dynamics in the helical filaments formed by RecA and Rad51 on DNA. Proc Natl Acad Sci U S A, 98, 8419-8424. 19. Sung, P. and Robberson, D.L. (1995) DNA strand exchange mediated by a RAD51-ssDNA nucleoprotein filament with polarity opposite to that of RecA. Cell, 82, 453-461. 20. Ogawa, T., Yu, X., Shinohara, A. and Egelman, E.H. (1993) Similarity of the yeast RAD51 filament to the bacterial RecA filament. Science, 259, 1896-1899. 21. Cox, M.M. (2003) The bacterial RecA protein as a motor protein. Annu Rev Microbiol, 57, 551-577. 22. Bianco, P.R., Tracy, R.B. and Kowalczykowski, S.C. (1998) DNA strand exchange proteins: a biochemical and physical comparison. Front Biosci, 3, D570-603. 23. Menetski, J.P., Bear, D.G. and Kowalczykowski, S.C. (1990) Stable DNA heteroduplex formation catalyzed by the Escherichia coli RecA protein in the absence of ATP hydrolysis. Proc Natl Acad Sci U S A, 87, 21-25. 24. Robertson, R.B., Moses, D.N., Kwon, Y., Chan, P., Chi, P., Klein, H., Sung, P. and Greene, E.C. (2009) Structural transitions within human Rad51 nucleoprotein filaments. Proc Natl Acad Sci U S A, 106, 12688-12693. 25. Hilario, J., Amitani, I., Baskin, R.J. and Kowalczykowski, S.C. (2009) Direct imaging of human Rad51 nucleoprotein dynamics on individual DNA molecules. Proc Natl Acad Sci U S A, 106, 361-368. 26. Chi, P., Van Komen, S., Sehorn, M.G., Sigurdsson, S. and Sung, P. (2006) Roles of ATP binding and ATP hydrolysis in human Rad51 recombinase function. DNA Repair (Amst), 5, 381-391. 27. Bugreev, D.V. and Mazin, A.V. (2004) Ca2+ activates human homologous recombination protein Rad51 by modulating its ATPase activity. Proc Natl Acad Sci U S A, 101, 9988-9993. 28. Connor, F., Bertwistle, D., Mee, P.J., Ross, G.M., Swift, S., Grigorieva, E., Tybulewicz, V.L. and Ashworth, A. (1997) Tumorigenesis and a DNA repair defect in mice with a truncating Brca2 mutation. Nat Genet, 17, 423-430. 29. Ludwig, T., Chapman, D.L., Papaioannou, V.E. and Efstratiadis, A. (1997) Targeted mutations of breast cancer susceptibility gene homologs in mice: lethal phenotypes of Brca1, Brca2, Brca1/Brca2, Brca1/p53, and Brca2/p53 nullizygous embryos. Genes Dev, 11, 1226-1241. 30. Sharan, S.K., Morimatsu, M., Albrecht, U., Lim, D.S., Regel, E., Dinh, C., Sands, A., Eichele, G., Hasty, P. and Bradley, A. (1997) Embryonic lethality and radiation hypersensitivity mediated by Rad51 in mice lacking Brca2. Nature, 386, 804-810. 31. Suzuki, A., de la Pompa, J.L., Hakem, R., Elia, A., Yoshida, R., Mo, R., Nishina, H., Chuang, T., Wakeham, A., Itie, A. et al. (1997) Brca2 is required for embryonic cellular proliferation in the mouse. Genes Dev, 11, 1242-1252. 32. Chen, J., Silver, D.P., Walpita, D., Cantor, S.B., Gazdar, A.F., Tomlinson, G., Couch, F.J., Weber, B.L., Ashley, T., Livingston, D.M. et al. (1998) Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells. Mol Cell, 2, 317-328. 33. Yuan, S.S., Lee, S.Y., Chen, G., Song, M., Tomlinson, G.E. and Lee, E.Y. (1999) BRCA2 is required for ionizing radiation-induced assembly of Rad51 complex in vivo. Cancer Res, 59, 3547-3551. 34. Godthelp, B.C., Artwert, F., Joenje, H. and Zdzienicka, M.Z. (2002) Impaired DNA damage-induced nuclear Rad51 foci formation uniquely characterizes Fanconi anemia group D1. Oncogene, 21, 5002-5005. 35. Moynahan, M.E., Pierce, A.J. and Jasin, M. (2001) BRCA2 is required for homology-directed repair of chromosomal breaks. Mol Cell, 7, 263-272. 36. Wong, A.K., Pero, R., Ormonde, P.A., Tavtigian, S.V. and Bartel, P.L. (1997) RAD51 interacts with the evolutionarily conserved BRC motifs in the human breast cancer susceptibility gene brca2. J Biol Chem, 272, 31941-31944. 37. Yang, H., Li, Q., Fan, J., Holloman, W.K. and Pavletich, N.P. (2005) The BRCA2 homologue Brh2 nucleates RAD51 filament formation at a dsDNA-ssDNA junction. Nature, 433, 653-657. 38. Jensen, R.B., Carreira, A. and Kowalczykowski, S.C. (2010) Purified human BRCA2 stimulates RAD51-mediated recombination. Nature, 467, 678-683. 39. Liu, J., Doty, T., Gibson, B. and Heyer, W.D. (2010) Human BRCA2 protein promotes RAD51 filament formation on RPA-covered single-stranded DNA. Nat Struct Mol Biol, 17, 1260-1262. 40. Thorslund, T., McIlwraith, M.J., Compton, S.A., Lekomtsev, S., Petronczki, M., Griffith, J.D. and West, S.C. (2010) The breast cancer tumor suppressor BRCA2 promotes the specific targeting of RAD51 to single-stranded DNA. Nat Struct Mol Biol, 17, 1263-1265. 41. Zhao, W., Vaithiyalingam, S., San Filippo, J., Maranon, D.G., Jimenez-Sainz, J., Fontenay, G.V., Kwon, Y., Leung, S.G., Lu, L., Jensen, R.B. et al. (2015) Promotion of BRCA2-Dependent Homologous Recombination by DSS1 via RPA Targeting and DNA Mimicry. Mol Cell, 59, 176-187. 42. Akamatsu, Y., Dziadkowiec, D., Ikeguchi, M., Shinagawa, H. and Iwasaki, H. (2003) Two different Swi5-containing protein complexes are involved in mating-type switching and recombination repair in fission yeast. Proc Natl Acad Sci U S A, 100, 15770-15775. 43. Akamatsu, Y., Tsutsui, Y., Morishita, T., Siddique, M.S., Kurokawa, Y., Ikeguchi, M., Yamao, F., Arcangioli, B. and Iwasaki, H. (2007) Fission yeast Swi5/Sfr1 and Rhp55/Rhp57 differentially regulate Rhp51-dependent recombination outcomes. EMBO J, 26, 1352-1362. 44. Haruta, N., Akamatsu, Y., Tsutsui, Y., Kurokawa, Y., Murayama, Y., Arcangioli, B. and Iwasaki, H. (2008) Fission yeast Swi5 protein, a novel DNA recombination mediator. DNA Repair (Amst), 7, 1-9. 45. Khasanov, F.K., Salakhova, A.F., Khasanova, O.S., Grishchuk, A.L., Chepurnaja, O.V., Korolev, V.G., Kohli, J. and Bashkirov, V.I. (2008) Genetic analysis reveals different roles of Schizosaccharomyces pombe sfr1/dds20 in meiotic and mitotic DNA recombination and repair. Curr Genet, 54, 197-211. 46. Haruta, N., Kurokawa, Y., Murayama, Y., Akamatsu, Y., Unzai, S., Tsutsui, Y. and Iwasaki, H. (2006) The Swi5-Sfr1 complex stimulates Rhp51/Rad51- and Dmc1-mediated DNA strand exchange in vitro. Nat Struct Mol Biol, 13, 823-830. 47. Kokabu, Y., Murayama, Y., Kuwabara, N., Oroguchi, T., Hashimoto, H., Tsutsui, Y., Nozaki, N., Akashi, S., Unzai, S., Shimizu, T. et al. (2011) Fission yeast Swi5-Sfr1 protein complex, an activator of Rad51 recombinase, forms an extremely elongated dogleg-shaped structure. J. Biol. Chem., 286, 43569-43576. 48. Kurokawa, Y., Murayama, Y., Haruta-Takahashi, N., Urabe, I. and Iwasaki, H. (2008) Reconstitution of DNA strand exchange mediated by Rhp51 recombinase and two mediators. PLoS Biol., 6, e88. 49. Akamatsu, Y. and Jasin, M. (2010) Role for the mammalian Swi5-Sfr1 complex in DNA strand break repair through homologous recombination. PLoS Genet, 6, e1001160. 50. Yuan, J. and Chen, J. (2011) The role of the human SWI5-MEI5 complex in homologous recombination repair. J. Biol. Chem., 286, 9888-9893. 51. Ellermeier, C., Schmidt, H. and Smith, G.R. (2004) Swi5 acts in meiotic DNA joint molecule formation in Schizosaccharomyces pombe. Genetics, 168, 1891-1898. 52. Hayase, A., Takagi, M., Miyazaki, T., Oshiumi, H., Shinohara, M. and Shinohara, A. (2004) A protein complex containing Mei5 and Sae3 promotes the assembly of the meiosis-specific RecA homolog Dmc1. Cell, 119, 927-940. 53. Tsubouchi, H. and Roeder, G.S. (2004) The budding yeast mei5 and sae3 proteins act together with dmc1 during meiotic recombination. Genetics, 168, 1219-1230. 54. Young, J.A., Hyppa, R.W. and Smith, G.R. (2004) Conserved and nonconserved proteins for meiotic DNA breakage and repair in yeasts. Genetics, 167, 593-605. 55. Martin-Castellanos, C., Blanco, M., Rozalen, A.E., Perez-Hidalgo, L., Garcia, A.I., Conde, F., Mata, J., Ellermeier, C., Davis, L., San-Segundo, P. et al. (2005) A large-scale screen in S. pombe identifies seven novel genes required for critical meiotic events. Curr Biol, 15, 2056-2062. 56. Ferrari, S.R., Grubb, J. and Bishop, D.K. (2009) The Mei5-Sae3 protein complex mediates Dmc1 activity in Saccharomyces cerevisiae. J Biol Chem, 284, 11766-11770. 57. Tsai, S.P., Su, G.C., Lin, S.W., Chung, C.I., Xue, X., Dunlop, M.H., Akamatsu, Y., Jasin, M., Sung, P. and Chi, P. (2012) Rad51 presynaptic filament stabilization function of the mouse Swi5-Sfr1 heterodimeric complex. Nucleic Acids Res, 40, 6558-6569. 58. Su, G.C., Chung, C.I., Liao, C.Y., Lin, S.W., Tsai, C.T., Huang, T., Li, H.W. and Chi, P. (2014) Enhancement of ADP release from the RAD51 presynaptic filament by the SWI5-SFR1 complex. Nucleic Acids Res, 42, 349-358. 59. Su, G.C., Yeh, H.Y., Lin, S.W., Chung, C.I., Huang, Y.S., Liu, Y.C., Lyu, P.C. and Chi, P. (2016) Role of the RAD51-SWI5-SFR1 Ensemble in homologous recombination. Nucleic Acids Res. 60. Flores-Rozas, H. and Kolodner, R.D. (2000) Links between replication, recombination and genome instability in eukaryotes. Trends Biochem Sci, 25, 196-200. 61. Haber, J.E. (1999) DNA recombination: the replication connection. Trends Biochem Sci, 24, 271-275. 62. Heyer, W.D., Ehmsen, K.T. and Liu, J. (2010) Regulation of homologous recombination in eukaryotes. Annu Rev Genet, 44, 113-139. 63. Klein, H.L. and Kreuzer, K.N. (2002) Replication, recombination, and repair: going for the gold. Mol Cell, 9, 471-480. 64. Petermann, E. and Helleday, T. (2010) Pathways of mammalian replication fork restart. Nat Rev Mol Cell Biol, 11, 683-687. 65. Hartlerode, A.J. and Scully, R. (2009) Mechanisms of double-strand break repair in somatic mammalian cells. Biochem J, 423, 157-168. 66. Klein, H.L. (2008) The consequences of Rad51 overexpression for normal and tumor cells. DNA Repair (Amst), 7, 686-693. 67. Moynahan, M.E. and Jasin, M. (2010) Mitotic homologous recombination maintains genomic stability and suppresses tumorigenesis. Nat Rev Mol Cell Biol, 11, 196-207. 68. Holthausen, J.T., Wyman, C. and Kanaar, R. (2010) Regulation of DNA strand exchange in homologous recombination. DNA Repair (Amst), 9, 1264-1272. 69. Krogh, B.O. and Symington, L.S. (2004) Recombination proteins in yeast. Annu Rev Genet, 38, 233-271. 70. Lisby, M. and Rothstein, R. (2009) Choreography of recombination proteins during the DNA damage response. DNA Repair (Amst), 8, 1068-1076. 71. Sung, P. (1994) Catalysis of ATP-dependent homologous DNA pairing and strand exchange by yeast RAD51 protein. Science, 265, 1241-1243. 72. Ristic, D., Modesti, M., van der Heijden, T., van Noort, J., Dekker, C., Kanaar, R. and Wyman, C. (2005) Human Rad51 filaments on double- and single-stranded DNA: correlating regular and irregular forms with recombination function. Nucleic Acids Res, 33, 3292-3302. 73. Robertson, R.B., Moses, D.N., Kwon, Y., Chan, P., Zhao, W., Chi, P., Klein, H., Sung, P. and Greene, E.C. (2009) Visualizing the disassembly of S. cerevisiae Rad51 nucleoprotein filaments. J Mol Biol, 388, 703-720. 74. Say, A.F., Ledford, L.L., Sharma, D., Singh, A.K., Leung, W.K., Sehorn, H.A., Tsubouchi, H., Sung, P. and Sehorn, M.G. (2011) The budding yeast Mei5-Sae3 complex interacts with Rad51 and preferentially binds a DNA fork structure. DNA Repair (Amst), 10, 586-594. 75. Chi, P., San Filippo, J., Sehorn, M.G., Petukhova, G.V. and Sung, P. (2007) Bipartite stimulatory action of the Hop2-Mnd1 complex on the Rad51 recombinase. Genes Dev, 21, 1747-1757. 76. Mazin, A.V., Alexeev, A.A. and Kowalczykowski, S.C. (2003) A novel function of Rad54 protein. Stabilization of the Rad51 nucleoprotein filament. J Biol Chem, 278, 14029-14036. 77. Van Komen, S., Petukhova, G., Sigurdsson, S., Stratton, S. and Sung, P. (2000) Superhelicity-driven homologous DNA pairing by yeast recombination factors Rad51 and Rad54. Mol Cell, 6, 563-572. 78. Solinger, J.A., Kiianitsa, K. and Heyer, W.D. (2002) Rad54, a Swi2/Snf2-like recombinational repair protein, disassembles Rad51:dsDNA filaments. Mol Cell, 10, 1175-1188. 79. Shah, P.P., Zheng, X., Epshtein, A., Carey, J.N., Bishop, D.K. and Klein, H.L. (2010) Swi2/Snf2-related translocases prevent accumulation of toxic Rad51 complexes during mitotic growth. Mol Cell, 39, 862-872. 80. Wiese, C., Dray, E., Groesser, T., San Filippo, J., Shi, I., Collins, D.W., Tsai, M.S., Williams, G.J., Rydberg, B., Sung, P. et al. (2007) Promotion of homologous recombination and genomic stability by RAD51AP1 via RAD51 recombinase enhancement. Mol Cell, 28, 482-490. 81. Modesti, M., Budzowska, M., Baldeyron, C., Demmers, J.A., Ghirlando, R. and Kanaar, R. (2007) RAD51AP1 is a structure-specific DNA binding protein that stimulates joint molecule formation during RAD51-mediated homologous recombination. Mol. Cell, 28, 468-481. 82. Neuman, K.C., Chadd, E.H., Liou, G.F., Bergman, K. and Block, S.M. (1999) Characterization of photodamage to Escherichia coli in optical traps. Biophys J, 77, 2856-2863. 83. Petukhova, G., Stratton, S. and Sung, P. (1998) Catalysis of homologous DNA pairing by yeast Rad51 and Rad54 proteins. Nature, 393, 91-94. 84. Kuwabara, N., Murayama, Y., Hashimoto, H., Kokabu, Y., Ikeguchi, M., Sato, M., Mayanagi, K., Tsutsui, Y., Iwasaki, H. and Shimizu, T. (2012) Mechanistic insights into the activation of Rad51-mediated strand exchange from the structure of a recombination activator, the Swi5-Sfr1 complex. Structure, 20, 440-449. 85. Saikusa, K., Kuwabara, N., Kokabu, Y., Inoue, Y., Sato, M., Iwasaki, H., Shimizu, T., Ikeguchi, M. and Akashi, S. (2013) Characterisation of an intrinsically disordered protein complex of Swi5-Sfr1 by ion mobility mass spectrometry and small-angle X-ray scattering. Analyst, 138, 1441-1449. 86. Cloud, V., Chan, Y.L., Grubb, J., Budke, B. and Bishop, D.K. (2012) Rad51 is an accessory factor for Dmc1-mediated joint molecule formation during meiosis. Science, 337, 1222-1225. 87. Mehta, A. and Haber, J.E. (2014) Sources of DNA double-strand breaks and models of recombinational DNA repair. Cold Spring Harb. Perspect. Biol., 6, a016428. 88. Heyer, W.D. (2015) Regulation of recombination and genomic maintenance. Cold Spring Harb Perspect Biol, 7, a016501. 89. Jasin, M. (2002) Homologous repair of DNA damage and tumorigenesis: the BRCA connection. Oncogene, 21, 8981-8993. 90. Venkitaraman, A.R. (2014) Cancer suppression by the chromosome custodians, BRCA1 and BRCA2. Science, 343, 1470-1475. 91. Liu, J., Ehmsen, K.T., Heyer, W.D. and Morrical, S.W. (2011) Presynaptic filament dynamics in homologous recombination and DNA repair. Crit. Rev. Biochem. Mol. Biol., 46, 240-270. 92. Zelensky, A., Kanaar, R. and Wyman, C. (2014) Mediators of homologous DNA pairing. Cold Spring Harb. Perspect. Biol., 6, a016451. 93. San Filippo, J., Chi, P., Sehorn, M.G., Etchin, J., Krejci, L. and Sung, P. (2006) Recombination mediator and Rad51 targeting activities of a human BRCA2 polypeptide. J Biol Chem, 281, 11649-11657. 94. Esashi, F., Galkin, V.E., Yu, X., Egelman, E.H. and West, S.C. (2007) Stabilization of RAD51 nucleoprotein filaments by the C-terminal region of BRCA2. Nat. Struct. Mol. Biol., 14, 468-474. 95. Shin, D.S., Pellegrini, L., Daniels, D.S., Yelent, B., Craig, L., Bates, D., Yu, D.S., Shivji, M.K., Hitomi, C., Arvai, A.S. et al. (2003) Full-length archaeal Rad51 structure and mutants: mechanisms for RAD51 assembly and control by BRCA2. EMBO J., 22, 4566-4576. 96. Davies, O.R. and Pellegrini, L. (2007) Interaction with the BRCA2 C terminus protects RAD51-DNA filaments from disassembly by BRC repeats. Nat. Struct. Mol. Biol., 14, 475-483. 97. Davies, A.A., Masson, J.Y., McIlwraith, M.J., Stasiak, A.Z., Stasiak, A., Venkitaraman, A.R. and West, S.C. (2001) Role of BRCA2 in control of the RAD51 recombination and DNA repair protein. Mol. Cell, 7, 273-282. 98. Yu, D.S., Sonoda, E., Takeda, S., Huang, C.L., Pellegrini, L., Blundell, T.L. and Venkitaraman, A.R. (2003) Dynamic control of Rad51 recombinase by self-association and interaction with BRCA2. Mol. Cell, 12, 1029-1041. 99. Pellegrini, L., Yu, D.S., Lo, T., Anand, S., Lee, M., Blundell, T.L. and Venkitaraman, A.R. (2002) Insights into DNA recombination from the structure of a RAD51-BRCA2 complex. Nature, 420, 287-293. 100. Okada, T. and Keeney, S. (2005) Homologous recombination: needing to have my say. Curr Biol, 15, R200-202. 101. Sheridan, S. and Bishop, D.K. (2006) Red-Hed regulation: recombinase Rad51, though capable of playing the leading role, may be relegated to supporting Dmc1 in budding yeast meiosis. Genes Dev, 20, 1685-1691. 102. Shinohara, A. and Shinohara, M. (2004) Roles of RecA homologues Rad51 and Dmc1 during meiotic recombination. Cytogenet Genome Res, 107, 201-207. 103. Bishop, D.K. (2012) Rad51, the lead in mitotic recombinational DNA repair, plays a supporting role in budding yeast meiosis. Cell Cycle, 11, 4105-4106. 104. Yang, S., Yu, X., Seitz, E.M., Kowalczykowski, S.C. and Egelman, E.H. (2001) Archaeal RadA protein binds DNA as both helical filaments and octameric rings. J Mol Biol, 314, 1077-1085. 105. Sheridan, S.D., Yu, X., Roth, R., Heuser, J.E., Sehorn, M.G., Sung, P., Egelman, E.H. and Bishop, D.K. (2008) A comparative analysis of Dmc1 and Rad51 nucleoprotein filaments. Nucleic Acids Res, 36, 4057-4066. 106. VanLoock, M.S., Yu, X., Yang, S., Lai, A.L., Low, C., Campbell, M.J. and Egelman, E.H. (2003) ATP-mediated conformational changes in the RecA filament. Structure, 11, 187-196. 107. Hilario, J. and Kowalczykowski, S.C. (2010) Visualizing protein-DNA interactions at the single-molecule level. Curr Opin Chem Biol, 14, 15-22. 108. Forget, A.L. and Kowalczykowski, S.C. (2010) Single-molecule imaging brings Rad51 nucleoprotein filaments into focus. Trends Cell Biol, 20, 269-276. 109. Hsu, H.F., Ngo, K.V., Chitteni-Pattu, S., Cox, M.M. and Li, H.W. (2011) Investigating Deinococcus radiodurans RecA protein filament formation on double-stranded DNA by a real-time single-molecule approach. Biochemistry, 50, 8270-8280. 110. Chen, Z., Yang, H. and Pavletich, N.P. (2008) Mechanism of homologous recombination from the RecA-ssDNA/dsDNA structures. Nature, 453, 489-484. 111. Rual, J.F., Venkatesan, K., Hao, T., Hirozane-Kishikawa, T., Dricot, A., Li, N., Berriz, G.F., Gibbons, F.D., Dreze, M., Ayivi-Guedehoussou, N. et al. (2005) Towards a proteome-scale map of the human protein-protein interaction network. Nature, 437, 1173-1178. 112. Baumann, P., Benson, F.E. and West, S.C. (1996) Human Rad51 protein promotes ATP-dependent homologous pairing and strand transfer reactions in vitro. Cell, 87, 757-766. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/49197 | - |
| dc.description.abstract | 同源重組酵素RAD51 會進行同源重組去修復DNA 雙股斷裂。RAD51 會形成核蛋白絲來去啟動同源重組反應。最近哺乳類細胞實驗指出SWI5 和 SFR1 會形成複合體並參與在RAD51 所主導的同源重組修復。為了探討哺乳類的SWI5-SFR1 在RAD51 所主導的同源重組修復的生化角色，我們建立了蛋白表現及純化的步驟得到老鼠SWI5-SFR1 蛋白複合體。經由我們的生化研究指出，SWI5-SFR1 會刺激RAD51 所進行的同源DNA 配對以及穩定RAD51 核蛋白絲。這樣的研究顯示出SWI5-SFR1 刺激RAD51 活性主要是來自於穩定RAD51 核蛋白絲的生成。RAD51
是ssDNA 依賴的ATP 水解酵素。ATP 結合會促進RAD51 核蛋白絲的形成和股交換活性。然而，由於ATP 水解和低的ADP 釋放速率,會使有活性的ATP 結合的RAD51 核蛋白絲變成沒有活性的ADP結合的RAD51 核蛋白絲。我們進一步發現，SWI5-SFR1 會促進RAD51 核蛋白絲的ADP 釋放。這代表SWI5-SFR1 可以協助RAD51 核蛋白絲處在有活性的ATP 結合態。此外，我們也更進一步闡明SWI5-SFR1 和RAD51 交互作用的模式和區域。我們發現SWI5-SFR1 主要是跟多聚體RAD51 有交互作用。另外，我們也找到SWI5 的F83 和L85 對於和RAD51的交互作用是必要的。更重要的是，對於刺激RAD51 的活性是需要SWI5-SFR1和RAD51 的彼此交互作用。我們的研究結果闡釋了SWI5-SFR1 複合體刺激RAD51所主導的同源去氧核醣核酸的作用機轉。 | zh_TW |
| dc.description.abstract | Homologous recombination (HR) mediated by RAD51 recombinase eliminates DNA double-strand breaks in the genome. RAD51 forms a nucleoprotein filament on single-stranded DNA (ssDNA), termed the presynaptic filament, to initiate homologous recombination. Cytological studies in mammal indicate that SWI5 and SFR1 form a complex and participate in RAD51-mediated recombination repair. To decipher the mechanistic role of mammal SWI5-SFR1 complex in RAD51-mediated HR, we established the expression and the purification procedure to obtain mouse SWI5-SFR1 protein complex. Our biochemical study showed that SWI5-SFR1 complex stimulates homologous DNA pairing by RAD51 and stabilizes the RAD51 presynaptic filament, demonstrating that the stimulation of RAD51 activity stems from the stabilization of RAD51 filament by SWI5-SFR1 complex. RAD51 is an ssDNA dependent ATPase. ATP binding promotes the formation of a functional RAD51 nucleoprotein filament and DNA stand exchange activity. However, owing to ATP hydrolysis and slow dissociation rate of ADP, active RAD51 filament is converted into an inactive RAD51-ADP-ssDNA filament. We further documented that SWI5-SFR1 acts by facilitating the release of ADP from the RAD51 presynaptic filament, indicating that SWI5-SFR1 helps maintain RAD51 presynaptic filament in its active ATP bound form. Furthermore, we determined the interaction mode and region between SWI5-SFR1 and RAD51. We found that SWI5-SFR1 preferentially interacts with oligomeric form of RAD51. Importantly, the residue F83 and L85 in C-terminal SWI5 of SWI5-SFR1 complex is essential for the interaction of RAD51. The interaction of SWI5-SFR1 to RAD51 is indispensable for stimulation of RAD51 activity. Our results thus provide the insight for the action mechanism of RAD51-mediated DNA exchange by SWI5-SFR1 complex. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T11:19:00Z (GMT). No. of bitstreams: 1 ntu-105-D00b46013-1.pdf: 60939001 bytes, checksum: 31e77ca623ded4134ce341ccf30206fe (MD5) Previous issue date: 2016 | en |
| dc.description.tableofcontents | 中文摘要………………………………………………………………………………...1
Abstract…………………………………………………………………………………2 Chapter 1. Literature Review and General Introduction (1) DNA damage response and double strand break repair…………………………...9 (2) Homologous recombination-mediated DNA repair……………………………...11 (3) RAD51 recombinase……………………………………………………………..12 (4) BRCA2…………………………………………………………………………...14 (5) SWI5-SFR1 complex…………………………………………………………….15 (6) Aim of study……………………………………………………………………..17 Chapter 2. The stabilization of RAD51 filament by SWI5-SFR1 complex A. Abstract………………………………………………………………………….19 B. Introduction……………………………………………………………………..20 C. Materials and Methods………………………………………………………....22 (1) DNA substrates…………………………………………………………………..22 (2) Plasmids………………………………………………………………………….23 (3) Protein expression and purification ……………………………………………..24 (4) Exonuclease I protection assay…………………………………………………..28 (5) DNA strand exchange reaction…………………………………………………..29 (6) Isothermal titration calorimetry………………………………………………….29 (7) Analytical ultracentrifugation……………………………………………………30 (8) Affinity pulldowns……………………………………………………………….31 (9) Topological assay to measure presynaptic filament turnover……………………31 (10) DNA mobility shift assay………………………………………………………32 D. Results……………………………………………………………………………33 (1) Mammalian SWI5, SFR1 and the SWI5-SFR1 complex…………………. …….33 (2) Biophysical characterization of the SWI5-SFR1 complex…………….. ……….33 (3) SWI5–SFR1 stimulates RAD51 recombinase activity…………………………..34 (4) Interaction of SWI5–SFR1 with RAD51………………………………………...35 (5) Stabilization of the RAD51 presynaptic filament by the SWI5-SFR1 complex……………………………………………………………………...........36 (6) A stabilized RAD51 presynaptic filament is unresponsive to SWI5-SFR1……..38 (7) The RSfp motif in SFR1 is inhibitory to SWI5–SFR1 function…………………39 4 E. Discussion……………………………………………………………………….41 (1) Physical and functional interactions of the mammalian SWI5-SFR1 complex with Rad51……………..…………………………………………………………41 (2) Comparison of the mouse SWI5–SFR1 complex with its Schizosaccharomyces pombe and Saccharomyces cerevisiae orthologs………………………..………..42 (3) The regulatory role of the RSfp motif in SFR1………………………………….43 (4) Other Rad51 accessory factors with a presynaptic filament maintenance role….44 Chapter 3. Enhancement of ADP release from RAD51 filament by SWI5-SFR1 complex A. Abstract………………………………………………………………………….46 B. Introduction……………………………………………………………………..47 C. Materials and Methods…………………………………………………………49 (1) DNA substrates…………………………………………………………………..49 (2) Plasmids………………………………………………………………………….50 (3) Protein expression and purification……………………………………………...51 (4) Affinity pulldowns……………………………………………………………….53 (5) DNA strand exchange reaction ……………………………………………….…53 (6) Exonuclease I protection assay…………………………………………………..54 (7) Nitrocellulose filter binding assay to monitor ADP release from RAD51 filament………………………………..…………………………………………..54 (8) Single-molecule optical tweezers……………..…………………………………57 (9) ATPase activity…………………………………………………………………..58 D. Results……………………………………………………………………………60 (1) Single-molecule optical tweezers measurement provides evidence for stabilization of RAD51-DNA nucleoprotein filaments by SWI5-SFR1……..…...60 (2) SWI5-SFR1 enhances ATP hydrolysis by the RAD51 presynaptic filament……62 (3) Enhancement of RAD51 ATPase activity requires a specific interaction of SWI5-SFR1 with RAD51…………………………………………......64 (4) SWI5-SFR1 facilitates ADP/ATP exchange in the RAD51 presynaptic filament………………………..…………………………………………………..64 (5) SWI5-SFR1 enhances ADP release from the RAD51 filament…………………66 (6) SWI5-SFR1 has no significant effect on ATP-binding affinity of RAD51 filament…………..………………………………………………………………..68 E. Discussion…………………………………………………………......................68 5 (1) The function of SWI5-SFR1 in RAD51-mediated HR………………………….68 (2) Implications for the yeast Swi5-Sfr1 orthologs………………………………….69 Chapter 4. The interaction of RAD51-SWI5-SFR1 in homologous recombination A. Abstract………………………………………………………………………….72 B. Introduction……………………………………………………………………...73 C. Materials and Methods…………………………………………………………75 (1) DNA substrates…………………………………………………………………..76 (2) Plasmids………………………………………………………………………….76 (3) Protein expression and purification…………………………………….……......77 (4) Gel filtration analysis…………………………………………………………….80 (5) Affinity pulldown………………………………………………………………..80 (6) Limited proteolysis………………………………………………………………81 (7) DNA strand exchange……………………………………………………………81 (8) Exonuclease I protection…………………………………………………………81 (9) Analytical ultracentrifugation……………………………………………………82 (10) Circular dichroism analysis…………………………………………………….82 (11) ATPase activity…………………………………………………………………83 (12) Electron microscopy……………………………………………………………83 D. Results……………………………………………………………………………84 (1) SWI5–SFR1 interacts with the oligomeric form of RAD51……….……………84 (2) The amino-terminal half of SFR1 is dispensable for complex formation with SWI5 and interaction with RAD51………………………………………….....86 (3) The carboxyl-terminal region of SWI5 is critically important for RAD51 interaction……………………………………………………………………......87 (4) Physical interaction is prerequisite for RAD51 activity regulated by SWI5– SFR1…………………………………….……………………………………..89 E. Discussion………………………………………………………………………..91 (1) The physical interaction is prerequisite for the enhancement of SWI5–SFR1 by RAD51……………..…………………………………………………………..91 (2) Differential interaction modes of RAD51 and SWI5–SFR1 from yeast to mammal………………………………………………………………………….92 (3) The implication of SWI5–SFR1 interacts with oligomeric form of RAD51…….93 Chapter 5. Conclusions and Perspectives A. Summary of Key Findings……………………………………………….……..94 6 B. Future Directions……………………………………………………………..…96 (1) Functional relationship of SWI5-SFR1, RAD51 and DMC1 in meiotic recombination…………..………………………………………………………96 (2) Structural analysis for the function of SWI5-SFR1 complex in RAD51- mediated HR……….…………………………………….……………………..98 (3) Single-molecule approach to determine the assembly and disassembly of RAD51 filaments by SWI5-SFR1 complex……………………………….100 (4) Searching for SWI5-SFR1 interacting partners……………………………102 Figures………………………………………………………………………………..104 Figure A. Molecular mechanism of homologous recombination. ……………………104 Figure B. Recombinase RAD51 filament and displacement loop (D-loop) formation.105 Figure C. The role of ATP hydrolysis and ATP binding of RAD51 filament ……….106 Figure D. The function of BRCA2 in the formation of RAD51 filament…………….107 Figure 1. Biophysical properties of the SWI5–SFR1 complex……………………….108 Figure 2. Sedimentation velocity analysis of SWI5-SFR1……………………………109 Figure 3. Promotion of RAD51-mediated DNA strand exchange by SWI5–SFR1…..110 Figure 4. SWI5–SFR1 complex but not SWI5 or SFR1 physically interacts with Rad51…………………………..………………………………………….112 Figure 5. Enhancement of RAD51-mediated DNA strand exchange by SWI5–SFR1.113 Figure 6. Stabilization of the RAD51 presynaptic filament by SWI5–SFR1…………114 Figure 7. RecA presynaptic filament is not stabilized by SWI5-SFR1……………….116 Figure 8. DNA topological experiment to examine the presynaptic filament stabilization activity of SWI5-SFR1………………………………………………..…..117 Figure 9. Presynaptic filament stabilization by AMP-PNP or Ca2+ alleviates dependence on SWI5-SFR1………………………………………………………..…..118 Figure 10. Functional significance of the RSfp motif in SFR1……………………….119 Figure 11. RAD51 presynaptic filament stabilization by the SWI5-dN104SFR1…....121 Figure 12. SWI5-SFR1 is devoid of DNA binding activity…………………………..122 Figure 13. SWI5-SFR1 stabilizes RAD51 filament…………………………………..123 Figure 14. Stabilization of the RAD51 filament by AMP-PNP………………………124 Figure 15. SWI5-SFR1 enhances RAD51 ATPase activity…………………………..125 Figure 16. The effect of SWI5-SFR1 on ATP hydrolysis by the presynaptic filament is specific for RAD51. …………………………………………………….126 Figure 17. Functional interactions between RAD51 and SWI5-SFR1 complex……..127 7 Figure 18. SWI5-SFR1 but not RAD51AP1 mediates ADP–ATP exchange of RAD51 filament..………...……………………………………………………….129 Figure 19. SWI5, SFR1, or SWI5-SFR1 complex are devoid of nucleotide binding activity………………..………………………………………………….130 Figure 20. SWI5-SFR1 expedites ADP release from the RAD51 filament…………..132 Figure 21. SWI5-SFR1 facilitates ADP release from the RAD51 filament…………..133 Figure 22. SWI5-SFR1 does not alter ATP-binding affinity of RAD51 presynaptic filament...…….…………………….…………………………………….134 Figure 23. Inhibition of RAD51-mediated ATP hydrolysis by Ca2+………………….135 Figure 24. Effects of SWI5-SFR1 on the functional attributes of the RAD51-dsDNA filament…..……….………………...……………………………………136 Figure 25. Model depicting the mechanistic action of SWI5-SFR1 on RAD51 filament…………..………………………………………………………137 Figure 26. Oligomeric status of RAD51 wild-type (WT) or RAD51 S208E/A209D (RAD51 SA/ED) with or without the presence of BRC4 was analyzed by gel filtration analyses.………………………………………………………....138 Figure 27. SWI5–SFR1 interacts with the oligomeric formof RAD51……………….139 Figure 28. GST-BRC4 physically interacts with RAD51 but not SWI5-SFR1………141 Figure 29. Oligomeric status of mouse RAD51 (mRAD51) wild-type (WT), F86E, or A190L/A192L was analyzed by gel filtration………………..…………….142 Figure 30. Functional characterization of SWI5–SFR1dN202 complex………………..143 Figure 31. Sedimentation velocity analysis of the SWI5-SFR1dN202 complex………..145 Figure 32. SWI5dC20–SFR1, SWI5dC9–SFR1 and SWI5FL/AA–SFR1 are defective in RAD51 interaction……………………………..………………………..146 Figure 33. Biophysical properties of SWI5 F83A/L85A-SFR1 mutant complex…….148 Figure 34. SWI5 F83A/L85A-SFR1 is functionally impaired………………………..149 Figure 35. Representative images of negatively stained RAD51 presynaptic filaments as observed by electron microscopy.……………………………………...…151 Figure 36. SWI5-SFR1 has no effect on the functional attributes mouse DMC1 recombinase……………………..……………………………………….152 Figure 37. Gray scale of the residual bitmap for AUC and constant obtained by ITC for SWI5-SFR1…………………………..………………………………….153 Figure 38. The structure of SFR1dN202-SWI5 complex by SAXS and molecule modeling…………………………………………………………………154 8 Figure 39. The mechanistic function of SWI5-SFR1 complex on RAD51-mediated homologous recombination…………...…………………………………155 Abbreviation…………………………………………………………………………156 References……………………………………………………………........................157 | |
| dc.language.iso | en | |
| dc.subject | ADP 釋放 | zh_TW |
| dc.subject | 同源重組 | zh_TW |
| dc.subject | DNA 雙股斷裂 | zh_TW |
| dc.subject | RAD51 核蛋白絲 | zh_TW |
| dc.subject | SWI5-SFR1 | zh_TW |
| dc.subject | ATP 水解 | zh_TW |
| dc.subject | DNA double-strand breaks | en |
| dc.subject | RAD51 presynaptic filament | en |
| dc.subject | Homologous recombination | en |
| dc.subject | ADP release | en |
| dc.subject | ATP hydrolysis | en |
| dc.subject | SWI5-SFR1 | en |
| dc.title | 探討SWI5-SFR1 複合體在RAD51 參與的去氧核醣核酸修復的生化機制 | zh_TW |
| dc.title | The mechanistic study of SWI5-SFR1 complex on RAD51-mediated DNA repair | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 104-2 | |
| dc.description.degree | 博士 | |
| dc.contributor.oralexamcommittee | 蔡明道(Ming-Daw Tsai),李弘文(Hung-Wen Li),鄧述諄(Shu-Chun Teng),呂平江(Ping-Chiang Lyu) | |
| dc.subject.keyword | 同源重組,DNA 雙股斷裂,RAD51 核蛋白絲,SWI5-SFR1,ATP 水解,ADP 釋放, | zh_TW |
| dc.subject.keyword | Homologous recombination,DNA double-strand breaks,RAD51 presynaptic filament,SWI5-SFR1,ATP hydrolysis,ADP release, | en |
| dc.relation.page | 166 | |
| dc.identifier.doi | 10.6342/NTU201603201 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2016-08-19 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科學研究所 | zh_TW |
| 顯示於系所單位： | 生化科學研究所 | |
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