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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 鄧述諄(Shu-Chun Teng) | |
| dc.contributor.author | Chia-Yin Lu | en |
| dc.contributor.author | 盧佳吟 | zh_TW |
| dc.date.accessioned | 2021-06-08T04:41:01Z | - |
| dc.date.copyright | 2009-09-15 | |
| dc.date.issued | 2009 | |
| dc.date.submitted | 2009-08-12 | |
| dc.identifier.citation | 1. Pastink, A. and Lohman, P.H. (1999) Repair and consequences of double-strand breaks in DNA. Mutation research, 428, 141-156.
2. Pastink, A., Eeken, J.C. and Lohman, P.H. (2001) Genomic integrity and the repair of double-strand DNA breaks. Mutation research, 480-481, 37-50. 3. van den Bosch, M., Lohman, P.H. and Pastink, A. (2002) DNA double-strand break repair by homologous recombination. Biological chemistry, 383, 873-892. 4. Valerie, K. and Povirk, L.F. (2003) Regulation and mechanisms of mammalian double-strand break repair. Oncogene, 22, 5792-5812. 5. West, S.C. (2003) Molecular views of recombination proteins and their control. Nature reviews, 4, 435-445. 6. Dudas, A. and Chovanec, M. (2004) DNA double-strand break repair by homologous recombination. Mutation research, 566, 131-167. 7. Hickson, I.D. (2003) RecQ helicases: caretakers of the genome. Nat Rev Cancer, 3, 169-178. 8. Hanada, K. and Hickson, I.D. (2007) Molecular genetics of RecQ helicase disorders. Cell Mol Life Sci, 64, 2306-2322. 9. Khakhar, R.R., Cobb, J.A., Bjergbaek, L., Hickson, I.D. and Gasser, S.M. (2003) RecQ helicases: multiple roles in genome maintenance. Trends in cell biology, 13, 493-501. 10. Yu, C.E., Oshima, J., Fu, Y.H., Wijsman, E.M., Hisama, F., Alisch, R., Matthews, S., Nakura, J., Miki, T., Ouais, S. et al. (1996) Positional cloning of the Werner's syndrome gene. Science (New York, N.Y, 272, 258-262. 11. Ellis, N.A., Groden, J., Ye, T.Z., Straughen, J., Lennon, D.J., Ciocci, S., Proytcheva, M. and German, J. (1995) The Bloom's syndrome gene product is homologous to RecQ helicases. Cell, 83, 655-666. 12. Kitao, S., Shimamoto, A., Goto, M., Miller, R.W., Smithson, W.A., Lindor, N.M. and Furuichi, Y. (1999) Mutations in RECQL4 cause a subset of cases of Rothmund-Thomson syndrome. Nature genetics, 22, 82-84. 13. Mimitou, E.P. and Symington, L.S. (2008) Sae2, Exo1 and Sgs1 collaborate in DNA double-strand break processing. Nature, 455, 770-774. 14. Zhu, Z., Chung, W.H., Shim, E.Y., Lee, S.E. and Ira, G. (2008) Sgs1 helicase and two nucleases Dna2 and Exo1 resect DNA double-strand break ends. Cell, 134, 981-994. 15. Schwartz, D.C. and Hochstrasser, M. (2003) A superfamily of protein tags: ubiquitin, SUMO and related modifiers. Trends in biochemical sciences, 28, 321-328. 16. Rog, O., Miller, K.M., Ferreira, M.G. and Cooper, J.P. (2009) Sumoylation of RecQ helicase controls the fate of dysfunctional telomeres. Mol Cell, 33, 559-569. 17. Kawabe, Y., Seki, M., Seki, T., Wang, W.S., Imamura, O., Furuichi, Y., Saitoh, H. and Enomoto, T. (2000) Covalent modification of the Werner's syndrome gene product with the ubiquitin-related protein, SUMO-1. The Journal of biological chemistry, 275, 20963-20966. 18. Eladad, S., Ye, T.Z., Hu, P., Leversha, M., Beresten, S., Matunis, M.J. and Ellis, N.A. (2005) Intra-nuclear trafficking of the BLM helicase to DNA damage-induced foci is regulated by SUMO modification. Human molecular genetics, 14, 1351-1365. 19. Branzei, D., Sollier, J., Liberi, G., Zhao, X., Maeda, D., Seki, M., Enomoto, T., Ohta, K. and Foiani, M. (2006) Ubc9- and mms21-mediated sumoylation counteracts recombinogenic events at damaged replication forks. Cell, 127, 509-522. 20. Bryan, T.M., Marusic, L., Bacchetti, S., Namba, M. and Reddel, R.R. (1997) The telomere lengthening mechanism in telomerase-negative immortal human cells does not involve the telomerase RNA subunit. Human molecular genetics, 6, 921-926. 21. Dunham, M.A., Neumann, A.A., Fasching, C.L. and Reddel, R.R. (2000) Telomere maintenance by recombination in human cells. Nature genetics, 26, 447-450. 22. Reddel, R.R., Bryan, T.M., Colgin, L.M., Perrem, K.T. and Yeager, T.R. (2001) Alternative lengthening of telomeres in human cells. Radiat Res, 155, 194-200. 23. Lundblad, V. and Blackburn, E.H. (1993) An alternative pathway for yeast telomere maintenance rescues est1- senescence. Cell, 73, 347-360. 24. Teng, S.C. and Zakian, V.A. (1999) Telomere-telomere recombination is an efficient bypass pathway for telomere maintenance in Saccharomyces cerevisiae. Molecular and cellular biology, 19, 8083-8093. 25. Cohen, H. and Sinclair, D.A. (2001) Recombination-mediated lengthening of terminal telomeric repeats requires the Sgs1 DNA helicase. Proc Natl Acad Sci U S A, 98, 3174-3179. 26. Teng, S.C., Chang, J., McCowan, B. and Zakian, V.A. (2000) Telomerase-independent lengthening of yeast telomeres occurs by an abrupt Rad50p-dependent, Rif-inhibited recombinational process. Mol Cell, 6, 947-952. 27. Tsai, H.J., Huang, W.H., Li, T.K., Tsai, Y.L., Wu, K.J., Tseng, S.F. and Teng, S.C. (2006) Involvement of topoisomerase III in telomere-telomere recombination. The Journal of biological chemistry, 281, 13717-13723. 28. Huang, P., Pryde, F.E., Lester, D., Maddison, R.L., Borts, R.H., Hickson, I.D. and Louis, E.J. (2001) SGS1 is required for telomere elongation in the absence of telomerase. Curr Biol, 11, 125-129. 29. Johnson, F.B., Marciniak, R.A., McVey, M., Stewart, S.A., Hahn, W.C. and Guarente, L. (2001) The Saccharomyces cerevisiae WRN homolog Sgs1p participates in telomere maintenance in cells lacking telomerase. The EMBO journal, 20, 905-913. 30. Rose, M.D., Winston, F., Hieter, P. (1990) Methods in Yeast Genetics. Cold Spring Harbor Laboratory, NY, Cold Spring Harbor. 31. Bahler, J., Wu, J.Q., Longtine, M.S., Shah, N.G., McKenzie, A., 3rd, Steever, A.B., Wach, A., Philippsen, P. and Pringle, J.R. (1998) Heterologous modules for efficient and versatile PCR-based gene targeting in Schizosaccharomyces pombe. Yeast, 14, 943-951. 32. Maeda, D., Seki, M., Onoda, F., Branzei, D., Kawabe, Y. and Enomoto, T. (2004) Ubc9 is required for damage-tolerance and damage-induced interchromosomal homologous recombination in S. cerevisiae. DNA repair, 3, 335-341. 33. Li, S.J. and Hochstrasser, M. (1999) A new protease required for cell-cycle progression in yeast. Nature, 398, 246-251. 34. Li, S.J. and Hochstrasser, M. (2000) The yeast ULP2 (SMT4) gene encodes a novel protease specific for the ubiquitin-like Smt3 protein. Molecular and cellular biology, 20, 2367-2377. 35. Schneider, B.L., Seufert, W., Steiner, B., Yang, Q.H. and Futcher, A.B. (1995) Use of polymerase chain reaction epitope tagging for protein tagging in Saccharomyces cerevisiae. Yeast, 11, 1265-1274. 36. Zhao, X. and Blobel, G. (2005) A SUMO ligase is part of a nuclear multiprotein complex that affects DNA repair and chromosomal organization. Proc Natl Acad Sci U S A, 102, 4777-4782. 37. Cheng, C.H., Lo, Y.H., Liang, S.S., Ti, S.C., Lin, F.M., Yeh, C.H., Huang, H.Y. and Wang, T.F. (2006) SUMO modifications control assembly of synaptonemal complex and polycomplex in meiosis of Saccharomyces cerevisiae. Genes & development, 20, 2067-2081. 38. Tsai, Y.L., Tseng, S.F., Chang, S.H., Lin, C.C. and Teng, S.C. (2002) Involvement of replicative polymerases, Tel1p, Mec1p, Cdc13p, and the Ku complex in telomere-telomere recombination. Molecular and cellular biology, 22, 5679-5687. 39. Prado, F. and Aguilera, A. (1995) Role of reciprocal exchange, one-ended invasion crossover and single-strand annealing on inverted and direct repeat recombination in yeast: different requirements for the RAD1, RAD10, and RAD52 genes. Genetics, 139, 109-123. 40. Gangloff, S., McDonald, J.P., Bendixen, C., Arthur, L. and Rothstein, R. (1994) The yeast type I topoisomerase Top3 interacts with Sgs1, a DNA helicase homolog: a potential eukaryotic reverse gyrase. Molecular and cellular biology, 14, 8391-8398. 41. Ulrich, H.D. (2009) The SUMO system: an overview. Methods in molecular biology (Clifton, N.J, 497, 3-16. 42. Johnson, E.S. and Blobel, G. (1999) Cell cycle-regulated attachment of the ubiquitin-related protein SUMO to the yeast septins. J Cell Biol, 147, 981-994. 43. Bennett, C.B., Lewis, L.K., Karthikeyan, G., Lobachev, K.S., Jin, Y.H., Sterling, J.F., Snipe, J.R. and Resnick, M.A. (2001) Genes required for ionizing radiation resistance in yeast. Nature genetics, 29, 426-434. 44. Watt, P.M., Hickson, I.D., Borts, R.H. and Louis, E.J. (1996) SGS1, a homologue of the Bloom's and Werner's syndrome genes, is required for maintenance of genome stability in Saccharomyces cerevisiae. Genetics, 144, 935-945. 45. Ohuchi, T., Seki, M., Branzei, D., Maeda, D., Ui, A., Ogiwara, H., Tada, S. and Enomoto, T. (2008) Rad52 sumoylation and its involvement in the efficient induction of homologous recombination. DNA repair, 7, 879-889. 46. Sacher, M., Pfander, B., Hoege, C. and Jentsch, S. (2006) Control of Rad52 recombination activity by double-strand break-induced SUMO modification. Nat Cell Biol, 8, 1284-1290. 47. Onoda, F., Seki, M., Miyajima, A. and Enomoto, T. (2001) Involvement of SGS1 in DNA damage-induced heteroallelic recombination that requires RAD52 in Saccharomyces cerevisiae. Mol Gen Genet, 264, 702-708. 48. Bernstein, K.A., Shor, E., Sunjevaric, I., Fumasoni, M., Burgess, R.C., Foiani, M., Branzei, D. and Rothstein, R. (2009) Sgs1 function in the repair of DNA replication intermediates is separable from its role in homologous recombinational repair. The EMBO journal, 28, 915-925. 49. Bryk, M., Banerjee, M., Murphy, M., Knudsen, K.E., Garfinkel, D.J. and Curcio, M.J. (1997) Transcriptional silencing of Ty1 elements in the RDN1 locus of yeast. Genes & development, 11, 255-269. 50. Smith, J.S. and Boeke, J.D. (1997) An unusual form of transcriptional silencing in yeast ribosomal DNA. Genes & development, 11, 241-254. 51. Lin, D.Y., Huang, Y.S., Jeng, J.C., Kuo, H.Y., Chang, C.C., Chao, T.T., Ho, C.C., Chen, Y.C., Lin, T.P., Fang, H.I. et al. (2006) Role of SUMO-interacting motif in Daxx SUMO modification, subnuclear localization, and repression of sumoylated transcription factors. Mol Cell, 24, 341-354. 52. Bischof, O., Kim, S.H., Irving, J., Beresten, S., Ellis, N.A. and Campisi, J. (2001) Regulation and localization of the Bloom syndrome protein in response to DNA damage. J Cell Biol, 153, 367-380. 53. Shen, T.H., Lin, H.K., Scaglioni, P.P., Yung, T.M. and Pandolfi, P.P. (2006) The mechanisms of PML-nuclear body formation. Mol Cell, 24, 331-339. 54. Xhemalce, B., Riising, E.M., Baumann, P., Dejean, A., Arcangioli, B. and Seeler, J.S. (2007) Role of SUMO in the dynamics of telomere maintenance in fission yeast. Proc Natl Acad Sci U S A, 104, 893-898. 55. Pebernard, S., Schaffer, L., Campbell, D., Head, S.R. and Boddy, M.N. (2008) Localization of Smc5/6 to centromeres and telomeres requires heterochromatin and SUMO, respectively. The EMBO journal, 27, 3011-3023. 56. Cobb, J.A., Bjergbaek, L., Shimada, K., Frei, C. and Gasser, S.M. (2003) DNA polymerase stabilization at stalled replication forks requires Mec1 and the RecQ helicase Sgs1. The EMBO journal, 22, 4325-4336. 57. Stewart, E., Chapman, C.R., Al-Khodairy, F., Carr, A.M. and Enoch, T. (1997) rqh1+, a fission yeast gene related to the Bloom's and Werner's syndrome genes, is required for reversible S phase arrest. The EMBO journal, 16, 2682-2692. 58. Lustig, A.J., Kurtz, S. and Shore, D. (1990) Involvement of the silencer and UAS binding protein RAP1 in regulation of telomere length. Science (New York, N.Y, 250, 549-553. 59. Pastor, M.D., Garcia-Yebenes, I., Fradejas, N., Perez-Ortiz, J.M., Mora-Lee, S., Tranque, P., Moro, M.A., Pende, M. and Calvo, S. (2009) mTOR/S6 Kinase pathway contributes to astrocyte survival to ischemia. The Journal of biological chemistry. 60. Wang, Z., Wang, M., Kar, S. and Carr, B.I. (2009) Involvement of ATM-mediated Chk1/2 and JNK kinase signaling activation in HKH40A-induced cell growth inhibition. Journal of cellular physiology. 61. Devault, A., Gueydon, E. and Schwob, E. (2008) Interplay between S-cyclin-dependent kinase and Dbf4-dependent kinase in controlling DNA replication through phosphorylation of yeast Mcm4 N-terminal domain. Molecular biology of the cell, 19, 2267-2277. 62. Henneke, G., Koundrioukoff, S. and Hubscher, U. (2003) Multiple roles for kinases in DNA replication. EMBO reports, 4, 252-256. 63. Ubersax, J.A., Woodbury, E.L., Quang, P.N., Paraz, M., Blethrow, J.D., Shah, K., Shokat, K.M. and Morgan, D.O. (2003) Targets of the cyclin-dependent kinase Cdk1. Nature, 425, 859-864. 64. Ptacek, J., Devgan, G., Michaud, G., Zhu, H., Zhu, X., Fasolo, J., Guo, H., Jona, G., Breitkreutz, A., Sopko, R. et al. (2005) Global analysis of protein phosphorylation in yeast. Nature, 438, 679-684. 65. Fricke, W.M., Kaliraman, V. and Brill, S.J. (2001) Mapping the DNA topoisomerase III binding domain of the Sgs1 DNA helicase. The Journal of biological chemistry, 276, 8848-8855. 66. Bayart, E., Dutertre, S., Jaulin, C., Guo, R.B., Xi, X.G. and Amor-Gueret, M. (2006) The Bloom syndrome helicase is a substrate of the mitotic Cdc2 kinase. Cell cycle (Georgetown, Tex, 5, 1681-1686. 67. Dutertre, S., Ababou, M., Onclercq, R., Delic, J., Chatton, B., Jaulin, C. and Amor-Gueret, M. (2000) Cell cycle regulation of the endogenous wild type Bloom's syndrome DNA helicase. Oncogene, 19, 2731-2738. 68. Naiki, T., Wakayama, T., Nakada, D., Matsumoto, K. and Sugimoto, K. (2004) Association of Rad9 with double-strand breaks through a Mec1-dependent mechanism. Molecular and cellular biology, 24, 3277-3285. 69. Lorincz, A.T. and Reed, S.I. (1986) Sequence analysis of temperature-sensitive mutations in the Saccharomyces cerevisiae gene CDC28. Molecular and cellular biology, 6, 4099-4103. 70. Bishop, A.C., Ubersax, J.A., Petsch, D.T., Matheos, D.P., Gray, N.S., Blethrow, J., Shimizu, E., Tsien, J.Z., Schultz, P.G., Rose, M.D. et al. (2000) A chemical switch for inhibitor-sensitive alleles of any protein kinase. Nature, 407, 395-401. 71. Schwob, E., Bohm, T., Mendenhall, M.D. and Nasmyth, K. (1994) The B-type cyclin kinase inhibitor p40SIC1 controls the G1 to S transition in S. cerevisiae. Cell, 79, 233-244. 72. Davies, S.L., North, P.S., Dart, A., Lakin, N.D. and Hickson, I.D. (2004) Phosphorylation of the Bloom's syndrome helicase and its role in recovery from S-phase arrest. Molecular and cellular biology, 24, 1279-1291. 73. Leng, M., Chan, D.W., Luo, H., Zhu, C., Qin, J. and Wang, Y. (2006) MPS1-dependent mitotic BLM phosphorylation is important for chromosome stability. Proc Natl Acad Sci U S A, 103, 11485-11490. 74. Davalos, A.R., Kaminker, P., Hansen, R.K. and Campisi, J. (2004) ATR and ATM-dependent movement of BLM helicase during replication stress ensures optimal ATM activation and 53BP1 focus formation. Cell cycle (Georgetown, Tex, 3, 1579-1586. 75. Hietakangas, V., Anckar, J., Blomster, H.A., Fujimoto, M., Palvimo, J.J., Nakai, A. and Sistonen, L. (2006) PDSM, a motif for phosphorylation-dependent SUMO modification. Proc Natl Acad Sci U S A, 103, 45-50. 76. Tremblay, A.M., Wilson, B.J., Yang, X.J. and Giguere, V. (2008) Phosphorylation-dependent sumoylation regulates estrogen-related receptor-alpha and -gamma transcriptional activity through a synergy control motif. Molecular endocrinology (Baltimore, Md, 22, 570-584. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/23082 | - |
| dc.description.abstract | 當RecQ DNA 解旋酶─BLM及WRN發生突變時，會導致基因體的不穩定、提早老化並有易罹患癌症的徵兆。酵母菌中的RecQ 解旋酶 Sgs1 以調控基因重組的方式來維持基因體的完整性。其他物種中的同源蛋白─BLM及WRN，已被發現會受到多種轉譯後修飾，如類泛素化(sumoylation)、磷酸化(phosphorylation)及乙醯化(acetylation)。本研究確定了Sgs1發生類泛素化的時機，並釐清這樣的修飾在DNA重組修復上所扮演的角色。我發現 Sgs1 類泛素化發生在Lysine621 的位置，且特別會在DNA雙股斷裂發生時進行這樣的修飾。Sgs1的類泛素化會促進端粒重組，但不影響Sgs1的其他功能，如DNA受損的修復、重組、調控top3基因突變造成的生長遲緩及rDNA的重組。我們的研究證實了Sgs1的類泛素化調控了端粒重組的結果。
另外，我們也發現Sgs1會被磷酸化，且受到細胞週期素依賴性蛋白激酶(Cdk1)及細胞週期的調控。我們發現Sgs1磷酸化的程度在S 期最多，而在G1時期則最少，在Cdk1受損時這樣的磷酸化變化則會消失。利用激酶活性偵測實驗，我們證實了Sgs1會直接地被Cdk1磷酸化。這份研究中我證明了Sgs1會受到類泛素化及磷酸化的修飾，並會將我的結果衍生以期能夠更了解這些修飾是怎樣影響Sgs1的功能。 | zh_TW |
| dc.description.abstract | Mutations in genes encoding WRN and BLM RecQ DNA helicases lead to genome instability, premature aging and cancer predisposition syndromes. The Saccharomyces cerevisiae Sgs1 RecQ helicase safeguards genome integrity through its function in DNA recombination. RecQ homologues, WRN and BLM were all previously shown to be undergoing several post-translational modifications (PTMs), such as sumoylation, phosphorylation and acetylation. In this report, we identify the conditions under which Sgs1 sumoylation is induced, and clarify the role of this modification in different types of recombinational repair. We found that the Lysine 621 residue is critical for sumoylation in vivo and in vitro. We demonstrate that Sgs1 is specifically sumoylated under the stress of double strand breaks (DSBs). Sumoylation of Sgs1 promotes telomere-telomere recombination. In contrast, sumoylation of Sgs1 is dispensable for other functions of Sgs1, including damage recovery, homologous recombination, regulation of top3 slow growth and rDNA recombination. Our observations indicate that sumoylation on Sgs1 modulates the outcome in telomere recombination.
Moreover, we also observed that Sgs1 is phosphorylated in a Cdk1- and cell cycle-dependent manner. We showed that Sgs1 is hyperphosphorylated during S phase and is usually under-phosphorylated in G1 stage. The Cdk1-crippling backgrounds led to diminishment of Sgs1 hyperphosphorylation during S phase. By in vitro kinase assay, I also demonstrated that Sgs1 is directly phosphorylated by Cdk1 in vitro. Here I provided solid evidence that Sgs1 is sumoylated and phosphorylated, and will apply my data to further understood the detail mechanism how these modifications regulate Sgs1 functions. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T04:41:01Z (GMT). No. of bitstreams: 1 ntu-98-R96445120-1.pdf: 7279774 bytes, checksum: c858a8aeff7d73652cda3fc355f0c2dc (MD5) Previous issue date: 2009 | en |
| dc.description.tableofcontents | 口試委員會審定書…………………………………………………… 2
致謝………………………………………………………………3 中文摘要………………………………………………………………..4 Abstract…………………………………………………………5 Contents…………………………………………………………….7 Chapetr1. Sumoylation of the WRN and BLM ortholog, Sgs1, modulates telomere-telomere recombination in the budding yeast….8 Introduction…………………………………………………………..9 Materials and Methods……………………………………………..12 Results………………………………………………………………..17 Discussion……………………………………………………………26 Chapter 2. Sgs1 is phosphorylated by Cdk1 in vivo and in vitro…...30 Introduction………………………………………....………………… 31 Materials and Methods…………………………..……………………..34 Results…………………………………………..…………………….. 37 Discussion………………………………..…………………………… 42 Tables………………………………………………………………….. 45 Figures………………………………………………………………..46 Reference……………………………………………………………63 | |
| dc.language.iso | en | |
| dc.title | 轉譯後修飾在酵母菌DNA解旋酶Sgs1功能上扮演的角色探討 | zh_TW |
| dc.title | Characterization of the roles of post-translational modifications of RecQ helicase, Sgs1p, in Saccharomyces cereveciae | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 97-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 張典顯(Tien-Hsien Chang),李財坤(Tsai-Kun Lee) | |
| dc.subject.keyword | DNA 解旋酶,雙股DNA斷裂,轉譯後修飾,端粒重組,細胞週期, | zh_TW |
| dc.subject.keyword | DNA helicase,DNA double strand break,post-translational modifications,telomere recombination,cell cycle, | en |
| dc.relation.page | 69 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2009-08-12 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 微生物學研究所 | zh_TW |
| 顯示於系所單位： | 微生物學科所 | |
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