請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/16173完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 鄧述諄 | |
| dc.contributor.author | Chia-Yu Chung | en |
| dc.contributor.author | 鍾佳妤 | zh_TW |
| dc.date.accessioned | 2021-06-07T18:03:48Z | - |
| dc.date.copyright | 2012-09-19 | |
| dc.date.issued | 2012 | |
| dc.date.submitted | 2012-07-30 | |
| dc.identifier.citation | Abraham, R.T. (2001). Cell cycle checkpoint signaling through the ATM and ATR kinases. Genes & development 15, 2177-2196.
Albuquerque, C.P., Smolka, M.B., Payne, S.H., Bafna, V., Eng, J., and Zhou, H. (2008). A multidimensional chromatography technology for in-depth phosphoproteome analysis. Molecular & cellular proteomics : MCP 7, 1389-1396. Armanios, M. (2009). Syndromes of telomere shortening. Annual review of genomics and human genetics 10, 45-61. Blankley, R.T., and Lydall, D. (2004). A domain of Rad9 specifically required for activation of Chk1 in budding yeast. J Cell Sci 117, 601-608. Brachmann, C.B., Davies, A., Cost, G.J., Caputo, E., Li, J.C., Hieter, P., and Boeke, J.D. (1998). Designer deletion strains derived from Saccharomyces cerevisiae S288C: a useful set of strains and plasmids for PCR-mediated gene disruption and other applications. Yeast 14, 115-132. Buchman, A.R., Lue, N.F., and Kornberg, R.D. (1988). Connections between Transcriptional Activators, Silencers, and Telomeres as Revealed by Functional-Analysis of a Yeast DNA-Binding Protein. Mol Cell Biol 8, 5086-5099. Buck, S.W., and Shore, D. (1995). Action of a Rap1 Carboxy-Terminal Silencing Domain Reveals an Underlying Competition between Hmr and Telomeres in Yeast. Genes & development 9, 370-384. Calado, R.T., and Young, N.S. (2009). Telomere diseases. The New England journal of medicine 361, 2353-2365. de Lange, T. (2009). How Telomeres Solve the End-Protection Problem. Science 326, 948-952. Devlin, C., Ticebaldwin, K., Shore, D., and Arndt, K.T. (1991). Rap1 Is Required for Bas1/Bas2-Dependent and Gcn4-Dependent Transcription of the Yeast His4 Gene. Mol Cell Biol 11, 3642-3651. Emili, A. (1998). MEC1-dependent phosphorylation of Rad9p in response to DNA damage. Molecular cell 2, 183-189. Feeser, E.A., and Wolberger, C. (2008). Structural and functional studies of the Rap1 C-terminus reveal novel separation-of-function mutants. Journal of molecular biology 380, 520-531. Garcia, C.K., Wright, W.E., and Shay, J.W. (2007). Human diseases of telomerase dysfunction: Insights into tissue aging. Nucleic Acids Res 35, 7406-7416. Giesman, D., Best, L., and Tatchell, K. (1991). The Role of Rap1 in the Regulation of the Mat-Alpha Locus. Mol Cell Biol 11, 1069-1079. Greenwell, P.W., Kronmal, S.L., Porter, S.E., Gassenhuber, J., Obermaier, B., and Petes, T.D. (1995). TEL1, a gene involved in controlling telomere length in S. cerevisiae, is homologous to the human ataxia telangiectasia gene. Cell 82, 823-829. Harley, C.B., Futcher, A.B., and Greider, C.W. (1990). Telomeres shorten during ageing of human fibroblasts. Nature 345, 458-460. Harrison, J.C., and Haber, J.E. (2006). Surviving the breakup: the DNA damage checkpoint. Annu Rev Genet 40, 209-235. Hsu, C.L., Chen, Y.S., Tsai, S.Y., Tu, P.J., Wang, M.J., and Lin, J.J. (2004). Interaction of Saccharomyces Cdc13p with Pol1p, Imp4p, Sir4p and Zds2p is involved in telomere replication, telomere maintenance and cell growth control. Nucleic Acids Res 32, 511-521. Johnston, M., and Davis, R.W. (1984). Sequences That Regulate the Divergent Gal1-Gal10 Promoter in Saccharomyces-Cerevisiae. Mol Cell Biol 4, 1440-1448. Kim, S.T., Lim, D.S., Canman, C.E., and Kastan, M.B. (1999). Substrate specificities and identification of putative substrates of ATM kinase family members. The Journal of biological chemistry 274, 37538-37543. Kolodner, R.D., Putnam, C.D., and Myung, K. (2002). Maintenance of genome stability in Saccharomyces cerevisiae. Science 297, 552-557. Kurtz, S., and Shore, D. (1991). RAP1 protein activates and silences transcription of mating-type genes in yeast. Genes & development 5, 616-628. Kyrion, G., Boakye, K.A., and Lustig, A.J. (1992). C-terminal truncation of RAP1 results in the deregulation of telomere size, stability, and function in Saccharomyces cerevisiae. Mol Cell Biol 12, 5159-5173. Kyrion, G., Liu, K., Liu, C., Lustig, A.J., and Lustig, A.J. (1993). Rap1 and Telomere Structure Regulate Telomere Position Effects in Saccharomyces-Cerevisiae. Genes & development 7, 1146-1159. Levy, D.L., and Blackburn, E.H. (2004). Counting of Rif1p and Rif2p on Saccharomyces cerevisiae telomeres regulates telomere length. Mol Cell Biol 24, 10857-10867. Lewis, K.A., and Wuttke, D.S. (2012). Telomerase and telomere-associated proteins: structural insights into mechanism and evolution. Structure 20, 28-39. Liang, C.Y., Hsu, P.H., Chou, D.F., Pan, C.Y., Wang, L.C., Huang, W.C., Tsai, M.D., and Lo, W.S. (2011). The histone H3K36 demethylase Rph1/KDM4 regulates the expression of the photoreactivation gene PHR1. Nucleic Acids Res 39, 4151-4165. Lieb, J.D., Liu, X., Botstein, D., and Brown, P.O. (2001). Promoter-specific binding of Rap1 revealed by genome-wide maps of protein-DNA association (vol 28, pg 327, 2001). Nat Genet 29, 100-100. Lundblad, V., and Szostak, J.W. (1989). A mutant with a defect in telomere elongation leads to senescence in yeast. Cell 57, 633-643. Lustig, A.J., Kurtz, S., and Shore, D. (1990). Involvement of the silencer and UAS binding protein RAP1 in regulation of telomere length. Science 250, 549-553. Ma, J.L., Lee, S.J., Duong, J.K., and Stern, D.F. (2006). Activation of the checkpoint kinase Rad53 by the phosphatidyl inositol kinase-like kinase Mec1. Journal of Biological Chemistry 281, 3954-3963. McEachern, M.J., Krauskopf, A., and Blackburn, E.H. (2000). Telomeres and their control. Annu Rev Genet 34, 331-358. McGee, J.S., Phillips, J.A., Chan, A., Sabourin, M., Paeschke, K., and Zakian, V.A. (2010). Reduced Rif2 and lack of Mec1 target short telomeres for elongation rather than double-strand break repair. Nature structural & molecular biology 17, 1438-1445. Moretti, P., Freeman, K., Coodly, L., and Shore, D. (1994). Evidence That a Complex of Sir Proteins Interacts with the Silencer and Telomere Binding-Protein Rap1. Genes & development 8, 2257-2269. Moretti, P., and Shore, D. (2001). Multiple interactions in sir protein recruitment by Rap1p at silencers and telomeres in yeast. Mol Cell Biol 21, 8082-8094. Morse, R.H. (2000). RAP, RAP, open up! New wrinkles for RAP1 in yeast. Trends in genetics : TIG 16, 51-53. Nyberg, K.A., Michelson, R.J., Putnam, C.W., and Weinert, T.A. (2002). Toward maintaining the genome: DNA damage and replication checkpoints. Annu Rev Genet 36, 617-656. O'Neill, T., Dwyer, A.J., Ziv, Y., Chan, D.W., Lees-Miller, S.P., Abraham, R.H., Lai, J.H., Hill, D., Shiloh, Y., Cantley, L.C., et al. (2000). Utilization of oriented peptide libraries to identify substrate motifs selected by ATM. The Journal of biological chemistry 275, 22719-22727. Palladino, F., Laroche, T., Gilson, E., Axelrod, A., Pillus, L., and Gasser, S.M. (1993). Sir3 and Sir4 Proteins Are Required for the Positioning and Integrity of Yeast Telomeres. Cell 75, 543-555. Pina, B., Fernandez-Larrea, J., Garcia-Reyero, N., and Idrissi, F.Z. (2003). The different (sur)faces of Rap1p. Molecular genetics and genomics : MGG 268, 791-798. Ritchie, K.B., Mallory, J.C., and Petes, T.D. (1999a). Interactions of TLC1 (which encodes the RNA subunit of telomerase), TEL1, and MEC1 in regulating telomere length in the yeast Saccharomyces cerevisiae. Mol Cell Biol 19, 6065-6075. Ritchie, K.B., Mallory, J.C., and Petes, T.D. (1999b). Interactions of TLC1 (which encodes the RNA subunit of telomerase), TEL1, and MEC1 in regulating telomere length in the yeast Saccharomyces cerevisiae. Mol Cell Biol 19, 6065-6075. Sanchez, Y., Desany, B.A., Jones, W.J., Liu, Q., Wang, B., and Elledge, S.J. (1996). Regulation of RAD53 by the ATM-like kinases MEC1 and TEL1 in yeast cell cycle checkpoint pathways. Science 271, 357-360. Shore, D. (1994). RAP1: a protean regulator in yeast. Trends in genetics : TIG 10, 408-412. Shore, D., and Bianchi, A. (2009). Telomere length regulation: coupling DNA end processing to feedback regulation of telomerase. The EMBO journal 28, 2309-2322. Smolka, M.B., Albuquerque, C.P., Chen, S.H., and Zhou, H. (2007). Proteome-wide identification of in vivo targets of DNA damage checkpoint kinases. Proceedings of the National Academy of Sciences of the United States of America 104, 10364-10369. Sweeney, F.D., Yang, F., Chi, A., Shabanowitz, J., Hunt, D.F., and Durocher, D. (2005). Saccharomyces cerevisiae Rad9 acts as a Mec1 adaptor to allow Rad53 activation. Curr Biol 15, 1364-1375. Takata, H., Kanoh, Y., Gunge, N., Shirahige, K., and Matsuura, A. (2004). Reciprocal association of the budding yeast ATM-related proteins Tel1 and Mec1 with telomeres in vivo. Molecular cell 14, 515-522. Tseng, S.F., Lin, J.J., and Teng, S.C. (2006). The telomerase-recruitment domain of the telomere binding protein Cdc13 is regulated by Mec1p/Tel1p-dependent phosphorylation. Nucleic Acids Res 34, 6327-6336. Vialard, J.E., Gilbert, C.S., Green, C.M., and Lowndes, N.F. (1998). The budding yeast Rad9 checkpoint protein is subjected to Mec1/Tel1-dependent hyperphosphorylation and interacts with Rad53 after DNA damage. Embo Journal 17, 5679-5688. Wotton, D., and Shore, D. (1997). A novel Rap1p-interacting factor, Rif2p, cooperates with Rif1p to regulate telomere length in Saccharomyces cerevisiae. Genes & development 11, 748-760. Wright, J.H., Gottschling, D.E., and Zakian, V.A. (1992). Saccharomyces telomeres assume a non-nucleosomal chromatin structure. Genes & development 6, 197-210. Yu, G.L., Bradley, J.D., Attardi, L.D., and Blackburn, E.H. (1990). In vivo alteration of telomere sequences and senescence caused by mutated Tetrahymena telomerase RNAs. Nature 344, 126-132. Zakian, V.A. (1996). Structure, function, and replication of Saccharomyces cerevisiae telomeres. Annu Rev Genet 30, 141-172. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/16173 | - |
| dc.description.abstract | Rap1為一DNA結合蛋白，並在染色體末端的保護及端粒長度的調控上扮演非常重要的角色。在端粒上，Rap1除了會與Sir proteins 作用造成Telomere Position Effect外，也會與Rif proteins結合調控端粒的長度，而在本篇研究中我們發現，位在Rap1 C端的絲胺酸731之磷酸化透過影響與其他蛋白的結合，進而影響端粒的長度調控，透過yeast two-hybrid system顯示，當絲胺酸731突變為丙氨酸因而無法被加上磷酸根時，則Rap1與Rif1之間的作用增強，與Sir3之間的作用下降，因此端粒變短；而當絲胺酸731突變為天冬胺酸模擬磷酸根的負電荷時，則Rap1與Rif1之間的作用下降，與Sir3之間的作用維持不變，使得端粒變長。另一方面，透過專一性偵測絲胺酸731磷酸根的抗體發現，此磷酸修飾會在MMS treatment後與YKU80 deletion的狀況下出現，並且發現Mec1及Tel1為此磷酸修飾的kinases，暗示此磷酸修飾在細胞週期中的端粒調控機制上扮演重要角色。 | zh_TW |
| dc.description.abstract | Rap1 is an important DNA binding protein that protects the ends of chromosomes and maintains the homeostatic length of telomeres. Rap1 works along with its interacting proteins, Rif1 and Rif2, to execute its function in telomere maintenance. In this study, we found that phosphorylations of Rap1 at serine 731 within the C-terminal protein-interaction domain can regulate the telomere length. Mutation of serine to alanine promotes its interaction with Rif1 but reduces its interaction with Sir3 and therefore causes telomere shortening. In contrast, mutation of serine to aspartatic acid decreases the interaction with Rif1 but has no effect on the interaction with Sir3 and thus lengthens the telomere. In addition, the phosphorylation of Rap1 was found to be recognized after MMS treatment or under the condition of YKU80 deletion, and Mec1 as well as Tel1 were shown to be the kinases for the phosphorylation. All these, imply an important role of this modification during cell cycle. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-07T18:03:48Z (GMT). No. of bitstreams: 1 ntu-101-R99445105-1.pdf: 4251095 bytes, checksum: b2cb2a799040235dcbe3650334489f7b (MD5) Previous issue date: 2012 | en |
| dc.description.tableofcontents | 口試委員會審定書 #
誌謝 1 中文摘要 2 ABSTRACT 3 CONTENTS 4 Chapter 1 Introduction 6 Chapter 2 Materials and Methods 10 2.1 Yeast Strains and Plasmids Construction 10 2.2 Southern Blot Analysis and Telomere Length Measurement 10 2.3 Yeast Two-hybrid Studies 10 2.4 In Vitro Kinase Assays 11 2.5 Antibodies and Western Blot Analysis 11 Chapter 3 Results 13 3.1 Posphorylation of Rap1-S731 Affected Telomere Length Regulation 13 3.2 Mutants Alter Rap1 Interactions with Other Proteins 13 3.3 Phosphorylation of Rap1-S731 Can Be Induced by MMS Treatment in Vivo 14 3.4 Mec1 and Tel1 Are the Kinases of the Rap1-S731 Phosphorylation 15 Chapter 4 Discussion 18 4.1 The Competition between Sir3 and Rif1 Is Regulated by Phosphorylation Modification 18 4.2 Mec1 and Tel1 Are the Kinases Responsible for Rap1-S731 19 4.3 The Model of Telomere Length Regulation by Phosphorylation of Rap1 Serine 731 20 Chapter 5 References 21 Chapter 6 Tables and Figures 29 6.1 Yeast Strains Used in This Study 29 6.2 Rap1 Serine 731 Mutation Results in Telomere Shortening In Vivo 31 6.3 Effects of Rap1 Mutations on Protein-Protein Interactions in a Yeast Two-Hybrid Assay 32 6.4 Phosphorylation of Rap1 Serine 731 Induced by MMS Treatment and YKU80 Deletion 34 6.5 In Vitro Kinase Assay of Mec1 and rap1 (615-827) 35 6.6 In Vitro Kinase Assay of Tel1 and rap1 (615-827) 37 6.7 In Vitro Kinase Assay of Rad53 and rap1 (615-827) 38 6.8 Mec1 and Tel1 Are the Kinases Responsible For the Phosphorylation of Rap1-S731 39 6.9 A Schematic Model for Potential Function of Rap1 Serine 731 Phosphorylation 41 | |
| dc.language.iso | en | |
| dc.title | "探討雙股端粒結合蛋白,Rap1,之磷酸化修飾在端粒延長機制之調控" | zh_TW |
| dc.title | Investigation of the function of phosphorylations on a double-stranded telomeric binding protein, Rap1, on telomere replication | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 100-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 林敬哲,李財坤 | |
| dc.subject.keyword | 端粒長度,Rap1,磷酸化,Mec1,Tel1, | zh_TW |
| dc.subject.keyword | Telomere length,Rap1,Phosphorylation,Mec1,Tel1, | en |
| dc.relation.page | 42 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2012-07-31 | |
| 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 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-101-1.pdf 目前未授權公開取用 | 4.15 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。