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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/80232完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 林甫容(Fu-Jung Lin) | |
| dc.contributor.author | Wei-Ting Chen | en |
| dc.contributor.author | 陳威廷 | zh_TW |
| dc.date.accessioned | 2022-11-24T03:02:58Z | - |
| dc.date.available | 2021-08-13 | |
| dc.date.available | 2022-11-24T03:02:58Z | - |
| dc.date.copyright | 2021-08-13 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-07-27 | |
| dc.identifier.citation | Ali, S. H., DeCaprio, J. A. (2001). Cellular transformation by SV40 large T antigen: interaction with host proteins. Paper presented at the Seminars in cancer biology. Anderson, S. L., Coli, R., Daly, I. W., Kichula, E. A., Rork, M. J., Volpi, S. A., . . . Rubin, B. Y. (2001). Familial dysautonomia is caused by mutations of the IKAP gene. The American Journal of Human Genetics, 68(3), 753-758. Axelrod, F. B. (2004). Familial dysautonomia. Muscle nerve, 29(3), 352-363. Azqueta, A., Collins, A. R. (2013). The essential comet assay: a comprehensive guide to measuring DNA damage and repair. Archives of toxicology, 87(6), 949-968. Balbous, A., Cortes, U., Guilloteau, K., Rivet, P., Pinel, B., Duchesne, M., . . . Bensadoun, R. J. (2016). A radiosensitizing effect of RAD51 inhibition in glioblastoma stem-like cells. BMC cancer, 16(1), 1-13. Berg, M., Ågesen, T. H., Thiis-Evensen, E., Merok, M. A., Teixeira, M. R., Vatn, M. H., . . . Lothe, R. A. (2010). Distinct high resolution genome profiles of early onset and late onset colorectal cancer integrated with gene expression data identify candidate susceptibility loci. Molecular cancer, 9(1), 1-14. Björk, G. R. (1995). Genetic dissection of synthesis and function of modified nucleosides in bacterial transfer RNA. Progress in nucleic acid research and molecular biology, 50, 263-338. Blank, M., Tang, Y., Yamashita, M., Burkett, S. S., Cheng, S. Y., Zhang, Y. E. (2012). A tumor suppressor function of Smurf2 associated with controlling chromatin landscape and genome stability through RNF20. Nature medicine, 18(2), 227. Boone, N., Loriod, B., Bergon, A., Sbai, O., Formisano-Tréziny, C., Gabert, J., . . . Axelrod, F. B. (2010). Olfactory stem cells, a new cellular model for studying molecular mechanisms underlying familial dysautonomia. PLoS One, 5(12), e15590. Burgess, R. C., Misteli, T. (2015). Not all DDRs are created equal: non-canonical DNA damage responses. cell, 162(5), 944-947. Callen, E., Zong, D., Wu, W., Wong, N., Stanlie, A., Ishikawa, M., . . . Mendez-Dorantes, C. (2020). 53BP1 enforces distinct pre-and post-resection blocks on homologous recombination. Molecular cell, 77(1), 26-38. e27. Carter, S. L., Eklund, A. C., Kohane, I. S., Harris, L. N., Szallasi, Z. (2006). A signature of chromosomal instability inferred from gene expression profiles predicts clinical outcome in multiple human cancers. Nature genetics, 38(9), 1043-1048. Chassé, H., Boulben, S., Costache, V., Cormier, P., Morales, J. (2017). Analysis of translation using polysome profiling. Nucleic acids research, 45(3), e15-e15. Chen, C.-C., Feng, W., Lim, P. X., Kass, E. M., Jasin, M. (2018). Homology-directed repair and the role of BRCA1, BRCA2, and related proteins in genome integrity and cancer. Annual review of cancer biology, 2, 313-336. Chen, J.-J., Silver, D., Cantor, S., Livingston, D. M., Scully, R. (1999). BRCA1, BRCA2, and Rad51 operate in a common DNA damage response pathway. Cancer research, 59(7 Supplement), 1752s-1756s. Chen, Y.-T., Hims, M. M., Shetty, R. S., Mull, J., Liu, L., Leyne, M., Slaugenhaupt, S. A. (2009). Loss of mouse Ikbkap, a subunit of elongator, leads to transcriptional deficits and embryonic lethality that can be rescued by human IKBKAP. Molecular and cellular biology, 29(3), 736-744. Creppe, C., Malinouskaya, L., Volvert, M.-L., Gillard, M., Close, P., Malaise, O., . . . Ormenese, S. (2009). Elongator controls the migration and differentiation of cortical neurons through acetylation of α-tubulin. cell, 136(3), 551-564. Cunningham, F., Fiebelkorn, S., Johnson, M., Meredith, C. (2011). A novel application of the Margin of Exposure approach: segregation of tobacco smoke toxicants. Food and chemical toxicology, 49(11), 2921-2933. Dauden, M. I., Jaciuk, M., Müller, C. W., Glatt, S. (2018). Structural asymmetry in the eukaryotic Elongator complex. FEBS letters, 592(4), 502-515. Dauden, M. I., Kosinski, J., Kolaj‐Robin, O., Desfosses, A., Ori, A., Faux, C., . . . Beck, M. (2017). Architecture of the yeast Elongator complex. EMBO reports, 18(2), 264-279. Davies, A. A., Masson, J.-Y., McIlwraith, M. J., Stasiak, A. Z., Stasiak, A., Venkitaraman, A. R., West, S. C. (2001). Role of BRCA2 in control of the RAD51 recombination and DNA repair protein. Molecular cell, 7(2), 273-282. Davoli, T., de Lange, T. (2012). Telomere-driven tetraploidization occurs in human cells undergoing crisis and promotes transformation of mouse cells. Cancer cell, 21(6), 765-776. De Cárcer, G., Malumbres, M. (2014). A centrosomal route for cancer genome instability. Nature cell biology, 16(6), 504-506. Dong, C., Lin, Z., Diao, W., Li, D., Chu, X., Wang, Z., . . . Long, J. (2015). The Elp2 subunit is essential for elongator complex assembly and functional regulation. Structure, 23(6), 1078-1086. Dong, J., Ren, Y., Zhang, T., Wang, Z., Ling, C. C., Li, G. C., . . . Wen, B. (2018). Inactivation of DNA-PK by knockdown DNA-PKcs or NU7441 impairs non-homologous end-joining of radiation-induced double strand break repair. Oncology reports, 39(3), 912-920. Erdel, F., Kratz, K., Willcox, S., Griffith, J. D., Greene, E. C., de Lange, T. (2017). Telomere recognition and assembly mechanism of mammalian shelterin. Cell reports, 18(1), 41-53. Esberg, A., Huang, B., Johansson, M. J., Byström, A. S. (2006). Elevated levels of two tRNA species bypass the requirement for elongator complex in transcription and exocytosis. Molecular cell, 24(1), 139-148. Ferguson, L. R., Chen, H., Collins, A. R., Connell, M., Damia, G., Dasgupta, S., . . . Amin, A. (2015). Genomic instability in human cancer: Molecular insights and opportunities for therapeutic attack and prevention through diet and nutrition. Paper presented at the Seminars in cancer biology. Fridman, J. S., Lowe, S. W. (2003). Control of apoptosis by p53. Oncogene, 22(56), 9030-9040. Frohloff, F., Fichtner, L., Jablonowski, D., Breunig, K. D., Schaffrath, R. (2001). Saccharomyces cerevisiae Elongator mutations confer resistance to the Kluyveromyces lactis zymocin. The EMBO journal, 20(8), 1993-2003. Frye, M., Watt, F. M. (2006). The RNA methyltransferase Misu (NSun2) mediates Myc-induced proliferation and is upregulated in tumors. Current Biology, 16(10), 971-981. George, L., Chaverra, M., Wolfe, L., Thorne, J., Close-Davis, M., Eibs, A., . . . Carlson, G. A. (2013). Familial dysautonomia model reveals Ikbkap deletion causes apoptosis of Pax3+ progenitors and peripheral neurons. Proceedings of the National Academy of Sciences, 110(46), 18698-18703. Giegé, R., Sissler, M., Florentz, C. (1998). Universal rules and idiosyncratic features in tRNA identity. Nucleic acids research, 26(22), 5017-5035. Glatt, S., Létoquart, J., Faux, C., Taylor, N. M., Séraphin, B., Müller, C. W. (2012). The Elongator subcomplex Elp456 is a hexameric RecA-like ATPase. Nature structural molecular biology, 19(3), 314. Glatt, S., Zabel, R., Kolaj-Robin, O., Onuma, O. F., Baudin, F., Graziadei, A., . . . Seraphin, B. (2016). Structural basis for tRNA modification by Elp3 from Dehalococcoides mccartyi. Nature structural molecular biology, 23(9), 794. Goffena, J., Lefcort, F., Zhang, Y., Lehrmann, E., Chaverra, M., Felig, J., . . . George, L. (2018). Elongator and codon bias regulate protein levels in mammalian peripheral neurons. Nature communications, 9(1), 1-10. Goldstein, M., Kastan, M. B. (2015). The DNA damage response: implications for tumor responses to radiation and chemotherapy. Annual review of medicine, 66, 129-143. Gupta, R., Somyajit, K., Narita, T., Maskey, E., Stanlie, A., Kremer, M., . . . Nussenzweig, A. (2018). DNA repair network analysis reveals shieldin as a key regulator of NHEJ and PARP inhibitor sensitivity. cell, 173(4), 972-988. e923. Hammel, M., Rey, M., Yu, Y., Mani, R. S., Classen, S., Liu, M., . . . Weinfeld, M. (2011). XRCC4 protein interactions with XRCC4-like factor (XLF) create an extended grooved scaffold for DNA ligation and double strand break repair. Journal of biological chemistry, 286(37), 32638-32650. Hanahan, D., Weinberg, R. A. (2011). Hallmarks of cancer: the next generation. cell, 144(5), 646-674. Hartmann, A., Agurell, E., Beevers, C., Brendler-Schwaab, S., Burlinson, B., Clay, P., . . . Thybaud, V. (2003). Recommendations for conducting the in vivo alkaline Comet assay. Mutagenesis, 18(1), 45-51. Hayflick, L. (1965). The limited in vitro lifetime of human diploid cell strains. Experimental cell research, 37(3), 614-636. Hopper, A. K., Phizicky, E. M. (2003). tRNA transfers to the limelight. Genes development, 17(2), 162-180. Huang, B., Johansson, M. J., Byström, A. S. (2005). An early step in wobble uridine tRNA modification requires the Elongator complex. Rna, 11(4), 424-436. Huang, X., El-Sayed, I. H., Qian, W., El-Sayed, M. A. (2006). Cancer cell imaging and photothermal therapy in the near-infrared region by using gold nanorods. Journal of the American Chemical Society, 128(6), 2115-2120. Jablonowski, D., Zink, S., Mehlgarten, C., Daum, G., Schaffrath, R. (2006). tRNAGlu wobble uridine methylation by Trm9 identifies Elongator's key role for zymocin‐induced cell death in yeast. Molecular microbiology, 59(2), 677-688. Jamil, S., Lam, I., Majd, M., Tsai, S.-H., Duronio, V. (2015). Etoposide induces cell death via mitochondrial-dependent actions of p53. Cancer cell international, 15(1), 1-11. Khongkow, P., Karunarathna, U., Khongkow, M., Gong, C., Gomes, A. R., Yagüe, E., . . . Man, E. P. (2014). FOXM1 targets NBS1 to regulate DNA damage-induced senescence and epirubicin resistance. Oncogene, 33(32), 4144-4155. Krappmann, D., Hatada, E. N., Tegethoff, S., Li, J., Klippel, A., Giese, K., . . . Scheidereit, C. (2000). The IκB kinase (IKK) complex is tripartite and contains IKKγ but not IKAP as a regular component. Journal of biological chemistry, 275(38), 29779-29787. Krogan, N. J., Greenblatt, J. F. (2001). Characterization of a six-subunit holo-elongator complex required for the regulated expression of a group of genes in Saccharomyces cerevisiae. Molecular and cellular biology, 21(23), 8203-8212. Lang, F., Li, X., Zheng, W., Li, Z., Lu, D., Chen, G., . . . Shi, P. (2017). CTCF prevents genomic instability by promoting homologous recombination-directed DNA double-strand break repair. Proceedings of the National Academy of Sciences, 114(41), 10912-10917. Li, Q., Fazly, A., Zhou, H., Huang, S., Zhang, Z., Stillman, B. (2009). The elongator complex interacts with PCNA and modulates transcriptional silencing and sensitivity to DNA damage agents. PLoS Genet, 5(10), e1000684. Lin, F.-J., Shen, L., Jang, C.-W., Falnes, P. Ø., Zhang, Y. (2013). Ikbkap/Elp1 deficiency causes male infertility by disrupting meiotic progression. PLoS Genet, 9(5), e1003516. Macefield, V. G., Norcliffe-Kaufmann, L., Gutiérrez, J., Axelrod, F. B., Kaufmann, H. (2011). Can loss of muscle spindle afferents explain the ataxic gait in Riley–Day syndrome? Brain, 134(11), 3198-3208. Montaldo, N. P., Bordin, D. L., Brambilla, A., Rösinger, M., Martin, S. L. F., Bjørås, K. Ø., . . . Olsen, L. C. (2019). Alkyladenine DNA glycosylase associates with transcription elongation to coordinate DNA repair with gene expression. Nature communications, 10(1), 1-13. Morini, E., Gao, D., Montgomery, C. M., Salani, M., Mazzasette, C., Krussig, T. A., . . . Gabbeta, V. (2019). ELP1 splicing correction reverses proprioceptive sensory loss in familial dysautonomia. The American Journal of Human Genetics, 104(4), 638-650. Moynahan, M. E., Pierce, A. J., Jasin, M. (2001). BRCA2 is required for homology-directed repair of chromosomal breaks. Molecular cell, 7(2), 263-272. Nelissen, H., Fleury, D., Bruno, L., Robles, P., De Veylder, L., Traas, J., . . . Van Lijsebettens, M. (2005). The elongata mutants identify a functional Elongator complex in plants with a role in cell proliferation during organ growth. Proceedings of the National Academy of Sciences, 102(21), 7754-7759. Nowak, M. A., Komarova, N. L., Sengupta, A., Jallepalli, P. V., Shih, I.-M., Vogelstein, B., Lengauer, C. (2002). The role of chromosomal instability in tumor initiation. Proceedings of the National Academy of Sciences, 99(25), 16226-16231. Nowsheen, S., Aziz, K., Luo, K., Deng, M., Qin, B., Yuan, J., . . . Ding, W. (2018). ZNF506-dependent positive feedback loop regulates H2AX signaling after DNA damage. Nature communications, 9(1), 1-11. Otero, G., Fellows, J., Li, Y., de Bizemont, T., Dirac, A. M., Gustafsson, C. M., . . . Svejstrup, J. Q. (1999). Elongator, a multisubunit component of a novel RNA polymerase II holoenzyme for transcriptional elongation. Molecular cell, 3(1), 109-118. Panda, A. C., Martindale, J. L., Gorospe, M. (2017). Polysome fractionation to analyze mRNA distribution profiles. Bio-protocol, 7(3). Phizicky, E. M., Hopper, A. K. (2010). tRNA biology charges to the front. Genes development, 24(17), 1832-1860. Plo, I., Laulier, C., Gauthier, L., Lebrun, F., Calvo, F., Lopez, B. S. (2008). AKT1 inhibits homologous recombination by inducing cytoplasmic retention of BRCA1 and RAD51. Cancer research, 68(22), 9404-9412. Quax, T. E., Claassens, N. J., Söll, D., van der Oost, J. (2015). Codon bias as a means to fine-tune gene expression. Molecular cell, 59(2), 149-161. Rapino, F., Close, P. (2018). Wobble uridine tRNA modification: a new vulnerability of refractory melanoma. Molecular cellular oncology, 5(6), e1513725. Rapino, F., Delaunay, S., Rambow, F., Zhou, Z., Tharun, L., De Tullio, P., . . . Piepers, J. (2018). Codon-specific translation reprogramming promotes resistance to targeted therapy. Nature, 558(7711), 605-609. Rodriguez, V., Chen, Y., Elkahloun, A., Dutra, A., Pak, E., Chandrasekharappa, S. (2007). Chromosome 8 BAC array comparative genomic hybridization and expression analysis identify amplification and overexpression of TRMT12 in breast cancer. Genes, chromosomes and cancer, 46(7), 694-707. Saito, Y., Kobayashi, J., Kanemaki, M. T., Komatsu, K. (2020). RIF1 controls replication initiation and homologous recombination repair in a radiation dose-dependent manner. Journal of Cell Science. Schaffrath, R., Leidel, S. A. (2017). Wobble uridine modifications–a reason to live, a reason to die?! RNA biology, 14(9), 1209-1222. Scully, R., Chen, J., Plug, A., Xiao, Y., Weaver, D., Feunteun, J., . . . Livingston, D. M. (1997). Association of BRCA1 with Rad51 in mitotic and meiotic cells. cell, 88(2), 265-275. Selvadurai, K., Wang, P., Seimetz, J., Huang, R. H. (2014). Archaeal Elp3 catalyzes tRNA wobble uridine modification at C5 via a radical mechanism. Nature chemical biology, 10(10), 810. Sfeir, A., De Lange, T. (2012). Removal of shelterin reveals the telomere end-protection problem. Science, 336(6081), 593-597. Sharp, P. M., Li, W.-H. (1986). An evolutionary perspective on synonymous codon usage in unicellular organisms. Journal of molecular evolution, 24(1-2), 28-38. Shrivastav, M., De Haro, L. P., Nickoloff, J. A. (2008). Regulation of DNA double-strand break repair pathway choice. Cell research, 18(1), 134-147. Sierzputowska-Gracz, H., Sochacka, E., Malkiewicz, A., Kuo, K., Gehrke, C. W., Agris, P. F. (1987). Chemistry and structure of modified uridines in the anticodon, wobble position of transfer RNA are determined by thiolation. Journal of the American Chemical Society, 109(23), 7171-7177. Simon, M. D., Pinter, S. F., Fang, R., Sarma, K., Rutenberg-Schoenberg, M., Bowman, S. K., . . . Lee, J. T. (2013). High-resolution Xist binding maps reveal two-step spreading during X-chromosome inactivation. Nature, 504(7480), 465-469. Slaugenhaupt, S. A., Blumenfeld, A., Gill, S. P., Leyne, M., Mull, J., Cuajungco, M. P., . . . Reznik, L. (2001). Tissue-specific expression of a splicing mutation in the IKBKAP gene causes familial dysautonomia. The American Journal of Human Genetics, 68(3), 598-605. Slaugenhaupt, S. A., Mull, J., Leyne, M., Cuajungco, M. P., Gill, S. P., Hims, M. M., . . . Gusella, J. F. (2004). Rescue of a human mRNA splicing defect by the plant cytokinin kinetin. Human molecular genetics, 13(4), 429-436. So, S., Davis, A. J., Chen, D. J. (2009). Autophosphorylation at serine 1981 stabilizes ATM at DNA damage sites. Journal of Cell Biology, 187(7), 977-990. Solozobova, V., Rolletschek, A., Blattner, C. (2009). Nuclear accumulation and activation of p53 in embryonic stem cells after DNA damage. BMC cell biology, 10(1), 1-11. Sprinzl, M., Horn, C., Brown, M., Ioudovitch, A., Steinberg, S. (1998). Compilation of tRNA sequences and sequences of tRNA genes. Nucleic acids research, 26(1), 148-153. Stucki, M., Clapperton, J. A., Mohammad, D., Yaffe, M. B., Smerdon, S. J., Jackson, S. P. (2005). MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks. cell, 123(7), 1213-1226. Torres, A. G., Batlle, E., de Pouplana, L. R. (2014). Role of tRNA modifications in human diseases. Trends in molecular medicine, 20(6), 306-314. Walker, J., Kwon, S. Y., Badenhorst, P., East, P., McNeill, H., Svejstrup, J. Q. (2011). Role of elongator subunit Elp3 in Drosophila melanogaster larval development and immunity. Genetics, 187(4), 1067-1075. Waszak, S. M., Giles, W., Gudenas, B. L., Smith, K. S., Forget, A., Kojic, M., . . . Indersie, E. (2020). Germline elongator mutations in sonic hedgehog medulloblastoma. Nature, 580(7803), 396-401. Winkler, G. S., Kristjuhan, A., Erdjument-Bromage, H., Tempst, P., Svejstrup, J. Q. (2002). Elongator is a histone H3 and H4 acetyltransferase important for normal histone acetylation levels in vivo. Proceedings of the National Academy of Sciences, 99(6), 3517-3522. Wittschieben, B. Ø., Otero, G., de Bizemont, T., Fellows, J., Erdjument-Bromage, H., Ohba, R., . . . Svejstrup, J. Q. (1999). A novel histone acetyltransferase is an integral subunit of elongating RNA polymerase II holoenzyme. Molecular cell, 4(1), 123-128. Xiao, Z., Dunn, E., Singh, K., Khan, I. S., Yannone, S. M., Cowan, M. J. (2009). A non-leaky Artemis-deficient mouse that accurately models the human severe combined immune deficiency phenotype, including resistance to hematopoietic stem cell transplantation. Biology of Blood and Marrow Transplantation, 15(1), 1-11. Xu, S., Zhan, M., Jiang, C., He, M., Yang, L., Shen, H., . . . Shi, Y. (2019). Genome-wide CRISPR screen identifies ELP5 as a determinant of gemcitabine sensitivity in gallbladder cancer. Nature communications, 10(1), 1-14. Yang, K.-T., Inoue, A., Lee, Y.-J., Jiang, C.-L., Lin, F.-J. (2019). Loss of Ikbkap/Elp1 in mouse oocytes causes spindle disorganization, developmental defects in preimplantation embryos and impaired female fertility. Scientific reports, 9(1), 1-10. Yates, L. R., Campbell, P. J. (2012). Evolution of the cancer genome. Nature Reviews Genetics, 13(11), 795-806. Zuccotti, P., Modelska, A. (2016). Studying the translatome with polysome profiling. In Post-Transcriptional Gene Regulation (pp. 59-69): Springer. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/80232 | - |
| dc.description.abstract | 基因組不穩定性對於癌症的形成有著相當大程度的影響，而在遺傳性癌症中，基因組的不穩定性往往起源於細胞DNA修復機制有受損。延伸因子(Elongator complex)為6種不同子單位所構成之複合物，而由Ikbkap基因所編碼的IKAP/Elp1為此延伸因子的子單位，其功能主要是維持延伸因子結構的穩定。先前研究已證實延伸因子會參與多項細胞內的生理反應，像是組蛋白以及tRNA的修飾，DNA的甲基化，以及細胞骨架的乙醯化等，缺少任何一個子單位均會使延伸因子功能喪失。我們利用缺乏Ikbkap基因的老鼠胚胎纖維母細胞(MEFs)來進行後續實驗，發現剔除Ikbkap基因會使細胞染色體較容易有斷裂的現象發生，剔除Ikbkap基因的MEFs其生長情況也有受損，同時表現出較高的細胞凋亡率。為了誘導細胞有雙股DNA斷裂，我們利用輻射以及藥物處理的方式，發現缺乏Ikbkap基因的MEFs有較多DNA斷裂沒有被修復，我們也更進一步發現缺乏Ikbkap基因主要是造成DNA同源重組修復受損。我們以免疫螢光染色證實剔除Ikbkap細胞中，參與同源重組修復步驟中的RAD51 foci形成數量較少，而RAD51蛋白表現量於缺乏Ikbkap基因的MEFs內確實有下降的趨勢，當我們於細胞內再表現RAD51蛋白則可以改善DNA的斷裂程度，綜合以上研究我們認為剔除Ikbkap基因造成的基因組不穩定性上升是起源於同源重組受損。 | zh_TW |
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| dc.description.tableofcontents | "中文摘要 iii ABSTRACT iv 代號與縮寫對照表 v 總目錄 viii 圖目錄 x 第一章 緒論 1 1.1 癌症 (Cancer) 1 1.2 基因組不穩定 (Genomic instability) 3 1.3 DNA損害反應 (DNA damage response) 3 1.4 DNA修復 (DNA repair) 5 1.4.1 同源重組 (Homology-directed repair, HDR) 7 1.4.2 非同源性末端接合 (Non-homologous end-joining, NHEJ) 7 1.5 延伸因子(Elongator Complex Protein) 8 1.5.1 Elongator complex protein 1 (Elp1) 9 1.5.2 Elongator complex protein 2 (Elp2) 11 1.5.3 Elongator complex protein 3 (Elp3) 11 1.5.4 Elongator complex protein 456 (Elp456) 11 1.6 tRNA修飾 (tRNA modification) 13 第二章 材料和方法 16 第一節 前言與實驗流程 16 第二節 實驗方法與步驟 18 2.1 細胞培養 18 2.2 結晶紫染色 (crystal violet staining) 22 2.3 細胞免疫螢光染色 (immunofluorescence) 23 2.4 細胞凋亡分析 26 2.5 RNA抽取 (RNA extraction) 27 2.6 西方墨點法 (western blotting) 29 2.7 多核醣體分析實驗 (polysome profiling) 33 2.8 彗星實驗 (comet assay) 38 2.9 蛋白質組分析實驗細胞樣品處理 41 第三章 實驗結果 42 3.1 Ikbkap/Elp1-depleted iMEF細胞的產生 42 3-2 Ikbkap基因的剔除會使iMEF細胞的生長受阻 43 3-3 缺乏Ikbkap/Elp1的iMEF在誘導DNA雙股鍵斷裂後有較高的細胞凋亡率 44 3-4 缺乏Ikbkap/Elp1的iMEF有較高的基因組不穩定性 46 3-5 Ikbkap/Elp1會影響細胞的DNA修復 47 3-6 缺乏Ikbkap/Elp1會使Rad51 filament的形成受損 49 3-7 在有DNA斷裂的情況下，缺乏Ikbkap/Elp1會使Rad51 mRNA的轉譯效率下降 51 3-8 於缺乏Ikbkap/Elp1的iMEF再表現人類RAD51可以減少DNA的斷裂程度 53 3-9 缺乏Ikbkap/Elp1造成大部分蛋白的表現量下降 55 第四章 問題與討論 69 4-1 使用iMEF細胞進行Elp1剔除實驗 69 4-2 Elp1於iMEF細胞內主要分布在細胞質 69 4-3 利用輻射或藥物誘導雙股DNA斷裂 70 4-4 剔除Elp1會提升細胞凋亡率 71 4-5 Rad51蛋白於同源重組中的修復機制 72 4-6 延伸因子影響DNA修復的機制 73 4-7 剔除Ikbkap/Elp1的iMEF細胞整體蛋白轉譯效率不會發生改變 75 4-8 剔除Ikbkap/Elp1降低iMEF細胞內大部分蛋白質的量 75 4-9 再表現人類RAD51蛋白對iMEF細胞的影響 78 第五章 結論 79 第六章 參考文獻 80 附錄 80 " | |
| dc.language.iso | zh-TW | |
| dc.subject | RAD51 | zh_TW |
| dc.subject | 基因組不穩定性 | zh_TW |
| dc.subject | 延伸因子 | zh_TW |
| dc.subject | Ikbkap基因 | zh_TW |
| dc.subject | DNA同源重組 | zh_TW |
| dc.subject | genomic instability | en |
| dc.subject | RAD51 | en |
| dc.subject | homology-directed DNA repair | en |
| dc.subject | Ikbkap gene | en |
| dc.subject | elongator complex | en |
| dc.title | Ikbkap/ Elp1藉由促進細胞進行DNA同源重組修復以預防基因組不穩定性上升 | zh_TW |
| dc.title | Ikbkap/ Elp1 prevents genomic instability by promoting homology-directed DNA repair | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 冀宏源(Hsin-Tsai Liu),陳律佑(Chih-Yang Tseng),吳青錫 | |
| dc.subject.keyword | 基因組不穩定性,延伸因子,Ikbkap基因,DNA同源重組,RAD51, | zh_TW |
| dc.subject.keyword | genomic instability,elongator complex,Ikbkap gene,homology-directed DNA repair,RAD51, | en |
| dc.relation.page | 106 | |
| dc.identifier.doi | 10.6342/NTU202101353 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2021-07-28 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科技學系 | zh_TW |
| 顯示於系所單位： | 生化科技學系 | |
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