請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/26718
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 鄧述諄(Shu-Chun Teng) | |
dc.contributor.author | Yu-Tai Su | en |
dc.contributor.author | 蘇祐代 | zh_TW |
dc.date.accessioned | 2021-06-08T07:22:20Z | - |
dc.date.copyright | 2011-10-07 | |
dc.date.issued | 2011 | |
dc.date.submitted | 2011-08-10 | |
dc.identifier.citation | Bianchi, A., Negrini, S., and Shore, D. (2004). Delivery of yeast telomerase to a DNA break depends on the recruitment functions of Cdc13 and Est1. Mol Cell 16, 139-146.
Chandra, A., Hughes, T.R., Nugent, C.I., and Lundblad, V. (2001). Cdc13 both positively and negatively regulates telomere replication. Genes Dev 15, 404-414. Conrad, M.N., Wright, J.H., Wolf, A.J., and Zakian, V.A. (1990). RAP1 protein interacts with yeast telomeres in vivo: overproduction alters telomere structure and decreases chromosome stability. Cell 63, 739-750. Diede, S.J., and Gottschling, D.E. (1999). Telomerase-mediated telomere addition in vivo requires DNA primase and DNA polymerases alpha and delta. Cell 99, 723-733. Evans, S.K., and Lundblad, V. (1999). Est1 and Cdc13 as comediators of telomerase access. Science 286, 117-120. Francisco, L., Wang, W., and Chan, C.S. (1994). Type 1 protein phosphatase acts in opposition to IpL1 protein kinase in regulating yeast chromosome segregation. Mol Cell Biol 14, 4731-4740. Garvik, B., Carson, M., and Hartwell, L. (1995). Single-stranded DNA arising at telomeres in cdc13 mutants may constitute a specific signal for the RAD9 checkpoint. Mol Cell Biol 15, 6128-6138. Grandin, N., Reed, S.I., and Charbonneau, M. (1997). Stn1, a new Saccharomyces cerevisiae protein, is implicated in telomere size regulation in association with Cdc13. Genes Dev 11, 512-527. Li, S., Makovets, S., Matsuguchi, T., Blethrow, J.D., Shokat, K.M., and Blackburn, E.H. (2009). Cdk1-dependent phosphorylation of Cdc13 coordinates telomere elongation during cell-cycle progression. Cell 136, 50-61. Marcand, S., Brevet, V., Mann, C., and Gilson, E. (2000). Cell cycle restriction of telomere elongation. Curr Biol 10, 487-490. Nugent, C.I., Bosco, G., Ross, L.O., Evans, S.K., Salinger, A.P., Moore, J.K., Haber, J.E., and Lundblad, V. (1998). Telomere maintenance is dependent on activities required for end repair of double-strand breaks. Curr Biol 8, 657-660. Nugent, C.I., Hughes, T.R., Lue, N.F., and Lundblad, V. (1996). Cdc13p: a single-strand telomeric DNA-binding protein with a dual role in yeast telomere maintenance. Science 274, 249-252. Pennock, E., Buckley, K., and Lundblad, V. (2001). Cdc13 delivers separate complexes to the telomere for end protection and replication. Cell 104, 387-396. Qi, H., and Zakian, V.A. (2000). The Saccharomyces telomere-binding protein Cdc13p interacts with both the catalytic subunit of DNA polymerase alpha and the telomerase-associated est1 protein. Genes Dev 14, 1777-1788. Ruchaud, S., Carmena, M., and Earnshaw, W.C. (2007). Chromosomal passengers: conducting cell division. Nat Rev Mol Cell Biol 8, 798-812. Shore, D. (1994). RAP1: a protean regulator in yeast. Trends Genet 10, 408-412. Taggart, A.K., Teng, S.C., and Zakian, V.A. (2002). Est1p as a cell cycle-regulated activator of telomere-bound telomerase. Science 297, 1023-1026. 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. Tseng, S.F., Shen, Z.J., Tsai, H.J., Lin, Y.H., and Teng, S.C. (2009). Rapid Cdc13 turnover and telomere length homeostasis are controlled by Cdk1-mediated phosphorylation of Cdc13. Nucleic Acids Res 37, 3602-3611. Vodenicharov, M.D., and Wellinger, R.J. (2006). DNA degradation at unprotected telomeres in yeast is regulated by the CDK1 (Cdc28/Clb) cell-cycle kinase. Mol Cell 24, 127-137. Weinert, T.A., and Hartwell, L.H. (1993). Cell cycle arrest of cdc mutants and specificity of the RAD9 checkpoint. Genetics 134, 63-80. Wellinger, R.J., Ethier, K., Labrecque, P., and Zakian, V.A. (1996). Evidence for a new step in telomere maintenance. Cell 85, 423-433. Wellinger, R.J., Wolf, A.J., and Zakian, V.A. (1993). Saccharomyces telomeres acquire single-strand TG1-3 tails late in S phase. Cell 72, 51-60. Wiley, E.A., and Zakian, V.A. (1995). Extra telomeres, but not internal tracts of telomeric DNA, reduce transcriptional repression at Saccharomyces telomeres. Genetics 139, 67-79. Wright, J.H., Gottschling, D.E., and Zakian, V.A. (1992). Saccharomyces telomeres assume a non-nucleosomal chromatin structure. Genes Dev 6, 197-210. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/26718 | - |
dc.description.abstract | 在真核生物中,染色體的末端由蛋白質和DNA形成的特殊結構,稱之為端粒。端粒可以保護染色體不受傷害以維持染色體的完整性,也可避免染色體末端和末端融合,另外,還可經由和端粒酶之間的交互作用影響DNA複製是否完全。我們實驗室先前的研究發現,在出芽酵母菌中Cdc13這個結合染色體末端單股DNA的蛋白,在細胞週期的S phase至G2 phase會被三種蛋白質激酶磷酸化,而這個磷酸化Cdc13的動作會進而誘發端粒酶的活性。然而,如何終止這個過程至今仍未有解答。因此,本篇研究內容即探討細胞中是如何減低端粒酶的活性,使整個週期能夠順利的完成,並回到G1 phase。Ipl1/Aurora是一種在M phase具有活性的蛋白質激酶,使用專一性偵測絲胺酸314磷酸根的抗體,發現Ipl1會影響Cdc13中絲胺酸314的磷酸化。在生物體內的表現型分析顯示出將Cdc13中可以被Ipl1磷酸化的序列突變會造成端粒長度方面的異常。這些結果證明Ipl1會影響Cdc13中端粒酶吸引區域的絲胺酸314的磷酸化,進而使端粒酶受到排斥而離開端粒,以藉此不再繼續端粒的複製延長。綜合以上,Cdc13參與了兩種磷酸化調控的機制,先是在S phase晚期時開始正向吸引端粒酶,而後在M phase時則是扮演負向排斥端粒酶的角色。 | zh_TW |
dc.description.abstract | Telomeres, the protein-DNA structures found at the natural ends of eukaryotic chromosomes, are required to protect chromosomes from degradation and end-to-end fusion and to facilitate their complete replication. Our previous studies discovered that Cdc13 specifically activates telomerase at the late S phase through three kinases, and this recruitment is inactivated at the late M phase. However, the pathway to attenuate telomerase at the M phase remains elusive in the telomere field. I therefore intend to identify the step to antagonize this telomerase recruitment process that allows cells to smoothly proceed to next G1 phase. IPL1 encodes an essential protein kinase whose function is required during the later part of each cell cycle. Here I showed that Ipl1/Aurora-dependent phosphorylation on S314 of Cdc13 is essential for repulsion of the yeast telomerase complex from telomeres. Thus, Cdc13 participates in two phospho-regulatory steps—first positive at the late S phase, and then negative at the M phase. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T07:22:20Z (GMT). No. of bitstreams: 1 ntu-100-R98445120-1.pdf: 2511994 bytes, checksum: 4bea12703bd87c33a0b691a4baf5176f (MD5) Previous issue date: 2011 | en |
dc.description.tableofcontents | 口試委員會審定書 #
誌謝 i 中文摘要 ii ABSTRACT iii CONTENTS iv Chapter 1 Introduction 1 Chapter 2 Materials and methods 4 2.1 Yeast strains and plasmids construction 4 2.2 Telomere length determination 4 2.3 Telomere healing assay 5 2.4 Immunoprecipitation, western blot analysis and cell cycle analysis 5 2.5 Inhibition of Ipl1 in ipl1-4 strains 6 2.6 Co-immunoprecipitation 6 2.7 Two-hybrid assay 7 Chapter 3 Results 8 3.1 Mass analysis of phosphorylated Cdc13 8 3.2 Cdc13 serine 314 to alanine mutation results in telomere lengthening 8 3.3 Ipl1 dependent phosphorylation of Cdc13 is maximal during M phase 9 3.4 ipl1-4 has no measurable effect on telomere length maintenance 10 3.5 Phosphorylation of Cdc13 serine 314 disrupts telomerase recruitment 10 3.6 Functional analysis of the interaction between Cdc13 mutants and Stn1 or Pol1 11 3.7 Serine 314 phosphorylation activity is altered by pre-existing phosphorylation at threonine 308 12 3.8 Ipl1-mediated phosphorylation of Cdc13 is not essential for telomere healing 13 Chapter 4 Discussion 14 Chapter 5 Figures 16 5.1 Mass analysis shows putative phosphorylation sites of Cdc13 16 5.2 Phosphorylation of Cdc13 serine 314 affects telomerase-dependent telomere replication 17 5.3 Ipl1-dependent phosphorylation of Cdc13 serine 314 occurs during M phase of cell cycle 18 5.4 ipl1-4 has no measurable effect on telomere length maintenance 20 5.5 Phosphorylation of Cdc13 serine 314 is necessary for efficient repulsion of telomerase complex from telomeres 21 5.6 Interaction of Cdc13 with Pol1 or Stn1 22 5.7 Pre-existing phosphorylation of Cdc13 threonine 308 promotes serine 314 phosphorylation 23 5.8 Quantitation of telomere addition frequency 24 5.9 A schematic model for potential function of Cdc13 serine 314 phosphorylation 25 REFERENCE 26 | |
dc.language.iso | en | |
dc.title | 有絲分裂後期經由Aurora磷酸化Cdc13以拮抗端粒酶之活性 | zh_TW |
dc.title | Aurora-dependent phosphorylation of Cdc13 antagonizes telomerase recruitment at M phase | en |
dc.type | Thesis | |
dc.date.schoolyear | 99-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 林敬哲(Jing-Jer Lin),李財坤(Tsai-Kun Li),詹迺立(Nei-Li Chan) | |
dc.subject.keyword | 端粒,磷酸化,端粒酶,吸引區域, | zh_TW |
dc.subject.keyword | telomere,phosphorylation,telomerase-recruitment domain, | en |
dc.relation.page | 28 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2011-08-10 | |
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-100-1.pdf 目前未授權公開取用 | 2.45 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。