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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 | Hao-Jhe Sun | en |
dc.contributor.author | 孫浩哲 | zh_TW |
dc.date.accessioned | 2021-06-17T01:38:21Z | - |
dc.date.available | 2022-09-08 | |
dc.date.copyright | 2017-09-08 | |
dc.date.issued | 2017 | |
dc.date.submitted | 2017-07-31 | |
dc.identifier.citation | Reference
Artandi SE, D. R. (2000). A critical role for telomeres in suppressing and facilitating carcinogenesis. In Curr Opin Genet Dev, pp. 10:39–46. Bryan TM, E. A., Dalla-Pozza L, Dunham MA, Reddel RR (1997). Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines. In Nat Med, pp. 3:1271–1274. Chen Q, I. A., Greider CW (2001). Two survivor pathways that allow growth in the absence of telomerase are generated by distinct telomere recombination events. In Mol Cell Biol, pp. 21:1819–1827. Dunham MA, N. A., Fasching CL, Reddel RR (2000). Telomere maintenance by recombination in human cells. In Nat Genet, pp. 26:447–450. Greider, C. W., and Blackburn, E. H. (1985). Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 43, 405-413. Huang P, P. F., Lester D et al (2001). SGS1 is required for telomere elongation in the absence of telomerase. In Curr Biol, pp. 11:125–129. Johnson FB, M. R., McVey M, Stewart SA, Hahn WC, Guarente L (2001). The Saccharomyces cerevisiae WRN homolog Sgs1p participates in telomere maintenance in cells lacking telomerase. In EMBO J, pp. 20:905–913. Li P, N. A. (2015). Inner nuclear envelope protein SUN1 plays a prominent role in mammalian mRNA export. In Nucleic Acids Res, pp. 16;43(20):9874-9888. Reddel RR, B. T., Colgin LM, Perrem KT, Yeager TR (2001). Alternative lengthening of telomeres in human cells. In Radiat Res, pp. 155:194–200. Roderick J O'Sullivan, N. A., Daniel H Lackner, Liana Oganesian, Candy Haggblom, Armelle Corpet, Genevieve Almouzni & Jan Karlseder (2014). Rapid induction of alternative lengthening of telomeres by depletion of the histone chaperone ASF1. In Nature Structural & Molecular Biology, pp. 21, 167–174. Singer MS, G. D. (1994). TLC1: template RNA component of Saccharomyces cerevisiae telomerase. In Science, pp. 266:404–409. Teng SC, C. J., McCowan B, Zakian VA (2000). Telomerase independent lengthening of yeast telomeres occurs by an abrupt Rad50p-dependent, Rif-inhibited recombinational process. In Mol Cell, pp. 6:947–952. Teng SC, Z. V. (1999). Telomere-telomere recombination is an efficient bypass pathway for telomere maintenance in Saccharomyces cerevisiae. In Mol Cell Biol, pp. 19:8083–8093. Tsai HJ, H. W., Li TK et al (2006). Involvement of topoisomerase III in telomere-telomere recombination. In J Biol Chem, pp. 281:13717–13723. Vega LR, M. M., Zakian VA (2003). Getting to the end: telomerase access in yeast and humans. In Nat Rev Mol Cell Biol, pp. 4:948–959. Wellinger, M., Wochele, J., Biollaz, S. M., and Ludwig, C. (2012). Online elemental analysis of process gases with ICP-OES: a case study on waste wood combustion. Waste Manag 32, 1843-1852. Wenshu Lua, f., Josef Gotzmannb, , , Lucia Sironic, Verena-Maren Jaegera, f, Maria Schneidera, f, Yvonne Lükea, Mathias Uhléne, Cristina Al-Khalili Szigyartoe, Andreas Brachnerb, Jan Ellenbergc, Roland Foisnerb, Angelika A. Noegela, d, Iakowos Karakesisogl (2008). Sun1 forms immobile macromolecular assemblies at the nuclear envelope. In Biochim Biophys Acta, pp. 1783(1712):2415-1726. doi: 1710.1016/j. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/67574 | - |
dc.description.abstract | 端粒的維持有助於染色體的穩定,端粒酶以DNA典型的複製方式使端粒延長。在癌細胞和酵母菌中,當缺乏端粒酶時,會利用替代性的重組機制來維持端粒。大部的癌細胞會表現端粒酶的活性,但有10-15%的癌細胞利用不需要端粒酶的路徑來生存,稱為替代性端粒延長(ALT)。在ALT細胞中已知端粒重組能延長端粒。在細胞週期中,許多的腳色會參與在端粒連結核膜。端粒重組時需要拓撲異構酶II和IIIα來解開拓撲壓力。為了觀察當細胞失去核膜與端粒的連結是否會影響端粒重組,我們分別選了會與RAP1和TRF2作用的SUN1和LaminA當作核膜上的目標。在ALT細胞缺乏SUN1或是Lamin A時會增加APB的形成,當表現RAP1和SUN1的融合蛋白時則會使APB的形成下降。綜合失去端粒連結和組蛋白分子伴侶ASF1的缺失可以使非ALT細胞的APB形成有加成性的增加。 | zh_TW |
dc.description.abstract | Telomere maintenance is required for chromosome stability, and telomeres are typically elongated by telomerase following DNA replication. In both tumor and yeast cells that lack telomerase, telomeres are maintained via an alternative recombination mechanism. While most cancer cell present telomerase activity, a particular population of cancers (10–15%) live with telomerase-independent pathway which is known as Alternative Lengthening of Telomeres (ALT). Telomere-telomere recombination is the pathway for telomere elongation in ALT cell. During cell cycle, telomeres tethered to the nuclear envelope and nuclear components may be involved in this process. To investigate whether telomere recombination would be affected in cells that loses telomeres tethering, we modulated SUN1 and Lamin A which interact with telomere binding proteins RAP1 and TRF2, respectively, as targets on nuclear envelop. Depletion of SUN1 or Lamin A increased ALT-associated promyelocytic leukaemia bodies (APBs) formation in ALT cells. Expression of a RAP1 and SUN1 fusion protein decreased APB signals. The combination of loosen telomere tethering and depletion of histone chaperone ASF1 synergistically induced the APB formation in non-ALT cancer cells. SUN1 or Lamin A depletion bypass the requirement of TOP3 for efficient telomere-telomere recombination. Altogether, these findings indicate that while this regular telomere territory may protect telomeres, it also displays a function to suppress telomere-telomere recombination. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T01:38:21Z (GMT). No. of bitstreams: 1 ntu-106-R02445135-1.pdf: 1522030 bytes, checksum: 6a8dae53831a6c037948e120f6590738 (MD5) Previous issue date: 2017 | en |
dc.description.tableofcontents | CONTENTS
口試委員會審定書. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . i 摘要. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ii ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iii TABLE OF CONTENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 MATERIALS & METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .4 Mammalian Cell Culture, Transfection, and Western Blotting . . . . . . . . . . . . . . . . . . 4 Immunofluorescence staining . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Plasmid Constructions and Viral Transduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 RNA Purification and Quantitative Reverse Transcription PCR (qRT-PCR) . . . . . . . . 6 RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .7 SUN1 and LMNA affect cell proliferation in both ALT cell and non-ALT cell . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Depletion of SUN1 or LMNA increased the formation of APBs in ALT cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Enhancement of nuclear envelope anchorage inhibits APB formation in ALT cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Depletion SUN1 or LMNA increased the APB formation in ASF1 depleted cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Depletion of nuclear envelope anchorage increased APB formation in ALT cells even in the absence of TOP3α. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 Knockdown of SUN1 or LMNA did not relieve the telomere silencing on the telomeric expressing genes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 FIGURES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 Fig.1: Depletion of SUN1 and Lamin A in U2OS and VA13 cells. Fig.2: SUN1 and LMNA affect cell proliferation in both ALT cell and non-ALT cell. Fig.3: Depletion of SUN1 or LMNA increased the formation of APBs in ALT cells. Fig.4: Enhancement of nuclear envelope anchorage inhibits APB formation in ALT cells. Fig.5: Depletion SUN1 or LMNA increased the APB formation in ASF1 depleted cells. Fig.6: Depletion of nuclear envelope anchorage increased APB formation in ALT cells even in the absence of TOP3α. Fig.7: Knockdown of SUN1 or LMNA did not relieve the telomere silencing on the telomeric expressing genes. REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 | |
dc.language.iso | en | |
dc.title | ALT細胞核膜上的端粒連結抑制端粒重組 | zh_TW |
dc.title | Nuclear envelope tethering suppresses telomere-telomere recombination in ALT cells | en |
dc.type | Thesis | |
dc.date.schoolyear | 105-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 林敬哲(Jing-Jer Lin),劉雅雯(Ya-Wen Liu),吳青錫 | |
dc.subject.keyword | 端粒重組,端粒連結,替代性端粒延長,SUN1,Lamin A, | zh_TW |
dc.subject.keyword | Telomere-telomere recombination,Telomere tethering,Alternative lengthening of telomeres,SUN1,Lamin A, | en |
dc.relation.page | 25 | |
dc.identifier.doi | 10.6342/NTU201702198 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2017-07-31 | |
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 |
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