請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/67112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 | Huan-Yi Tseng | en |
| dc.contributor.author | 曾煥義 | zh_TW |
| dc.date.accessioned | 2021-06-17T01:20:16Z | - |
| dc.date.available | 2022-08-14 | |
| dc.date.copyright | 2017-08-14 | |
| dc.date.issued | 2017 | |
| dc.date.submitted | 2017-08-10 | |
| dc.identifier.citation | Abdel-Fattah, W., Jablonowski, D., Di Santo, R., Thuring, K. L., Scheidt, V., Hammermeister, A., Ten Have, S., Helm, M., Schaffrath, R., & Stark, M. J. (2015). Phosphorylation of Elp1 by Hrr25 is required for elongator-dependent tRNA modification in yeast. PLoS Genet, 11(1), e1004931.
Ali, S. H., & DeCaprio, J. A. (2001). Cellular transformation by SV40 large T antigen: interaction with host proteins. Semin Cancer Biol, 11(1), 15-23. Altieri, F., Grillo, C., Maceroni, M., & Chichiarelli, S. (2008). DNA damage and repair: from molecular mechanisms to health implications. Antioxid Redox Signal, 10(5), 891-937. Ames, B. N. (1989). Endogenous oxidative DNA damage, aging, and cancer. Free Radic Res Commun, 7(3-6), 121-128. Attardi, L. D., de Vries, A., & Jacks, T. (2004). Activation of the p53-dependent G1 checkpoint response in mouse embryo fibroblasts depends on the specific DNA damage inducer. Oncogene, 23(4), 973-980. Axelrod, F. B., Hilz, M. J., Berlin, D., Yau, P. L., Javier, D., Sweat, V., Bruehl, H., & Convit, A. (2010). Neuroimaging supports central pathology in familial dysautonomia. Journal of Neurology, 257(2), 198-206. Axelrod, F. B., Krey, L., Glickstein, J. S., Allison, J. W., & Friedman, D. (1995). Preliminary-Observations on the Use of Midodrine in Treating Orthostatic Hypotension in Familial Dysautonomia. Journal of the Autonomic Nervous System, 55(1-2), 29-35. Axelrod, F. B., Nachtigal, R., & Dancis, J. (1974). Familial dysautonomia: diagnosis, pathogenesis and management. Adv Pediatr, 21, 75-96. Bachrati, C. Z., & Hickson, I. D. (2003). RecQ helicases: suppressors of tumorigenesis and premature aging. Biochem J, 374(Pt 3), 577-606. Bartkova, J., Horejsi, Z., Koed, K., Kramer, A., Tort, F., Zieger, K., Guldberg, P., Sehested, M., Nesland, J. M., Lukas, C., Orntoft, T., Lukas, J., & Bartek, J. (2005). DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature, 434(7035), 864-870. Bean, L. J., & Stark, G. R. (2002). Regulation of the accumulation and function of p53 by phosphorylation of two residues within the domain that binds to Mdm2. J Biol Chem, 277(3), 1864-1871. Begley, U., Dyavaiah, M., Patil, A., Rooney, J. P., DiRenzo, D., Young, C. M., Conklin, D. S., Zitomer, R. S., & Begley, T. J. (2007). Trm9-catalyzed tRNA modifications link translation to the DNA damage response. Mol Cell, 28(5), 860-870. Benchimol, S., Pim, D., & Crawford, L. (1982). Radioimmunoassay of the cellular protein p53 in mouse and human cell lines. EMBO J, 1(9), 1055-1062. Bennett, C. B., Lewis, L. K., Karthikeyan, G., Lobachev, K. S., Jin, Y. H., Sterling, J. F., Snipe, J. R., & Resnick, M. A. (2001). Genes required for ionizing radiation resistance in yeast. Nature Genetics, 29(4), 426-434. Berger, M. F., Hodis, E., Heffernan, T. P., Deribe, Y. L., Lawrence, M. S., Protopopov, A., Ivanova, E., Watson, I. R., Nickerson, E., Ghosh, P., Zhang, H., Zeid, R., Ren, X., Cibulskis, K., Sivachenko, A. Y., Wagle, N., Sucker, A., Sougnez, C., Onofrio, R., Ambrogio, L., Auclair, D., Fennell, T., Carter, S. L., Drier, Y., Stojanov, P., Singer, M. A., Voet, D., Jing, R., Saksena, G., Barretina, J., Ramos, A. H., Pugh, T. J., Stransky, N., Parkin, M., Winckler, W., Mahan, S., Ardlie, K., Baldwin, J., Wargo, J., Schadendorf, D., Meyerson, M., Gabriel, S. B., Golub, T. R., Wagner, S. N., Lander, E. S., Getz, G., Chin, L., & Garraway, L. A. (2012). Melanoma genome sequencing reveals frequent PREX2 mutations. Nature, 485(7399), 502-506. Bergeron, J., Benlimame, N., Zeng-Rong, N., Xiao, D., Scrivens, P. J., Koromilas, A. E., & Alaoui-Jamali, M. A. (2000). Identification of the interferon-inducible double-stranded RNA-dependent protein kinase as a regulator of cellular response to bulky adducts. Cancer Res, 60(24), 6800-6804. Bernstein, C., Holubec, H., Bhattacharyya, A. K., Nguyen, H., Payne, C. M., Zaitlin, B., & Bernstein, H. (2011). Carcinogenicity of deoxycholate, a secondary bile acid. Arch Toxicol, 85(8), 863-871. Biedermann, K. A., Sun, J. R., Giaccia, A. J., Tosto, L. M., & Brown, J. M. (1991). scid mutation in mice confers hypersensitivity to ionizing radiation and a deficiency in DNA double-strand break repair. Proc Natl Acad Sci U S A, 88(4), 1394-1397. Blumenfeld, A., Slaugenhaupt, S. A., Axelrod, F. B., Lucente, D. E., Maayan, C., Liebert, C. B., Ozelius, L. J., Trofatter, J. A., Haines, J. L., Breakefield, X. O., & et al. (1993). Localization of the gene for familial dysautonomia on chromosome 9 and definition of DNA markers for genetic diagnosis. Nat Genet, 4(2), 160-164. Blumenfeld, A., Slaugenhaupt, S. A., Liebert, C. B., Temper, V., Maayan, C., Gill, S., Lucente, D. E., Idelson, M., MacCormack, K., Monahan, M. A., Mull, J., Leyne, M., Mendillo, M., Schiripo, T., Mishori, E., Breakefield, X., Axelrod, F. B., & Gusella, J. F. (1999). Precise genetic mapping and haplotype analysis of the familial dysautonomia gene on human chromosome 9q31. Am J Hum Genet, 64(4), 1110-1118. Borges, H. L., Linden, R., & Wang, J. Y. (2008). DNA damage-induced cell death: lessons from the central nervous system. Cell Res, 18(1), 17-26. Bouska, A., Lushnikova, T., Plaza, S., & Eischen, C. M. (2008). Mdm2 promotes genetic instability and transformation independent of p53. Mol Cell Biol, 28(15), 4862-4874. Brummelkamp, T. R., Bernards, R., & Agami, R. (2002). A system for stable expression of short interfering RNAs in mammalian cells. Science, 296(5567), 550-553. Budanov, A. V., & Karin, M. (2008). p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling. Cell, 134(3), 451-460. Cahill, D. P., Kinzler, K. W., Vogelstein, B., & Lengauer, C. (1999). Genetic instability and darwinian selection in tumours. Trends Cell Biol, 9(12), M57-60. Casavant, N. C., Luo, M. H., Rosenke, K., Winegardner, T., Zurawska, A., & Fortunato, E. A. (2006). Potential role for p53 in the permissive life cycle of human cytomegalovirus. J Virol, 80(17), 8390-8401. Cheishvili, D., Maayan, C., Cohen-Kupiec, R., Lefler, S., Weil, M., Ast, G., & Razin, A. (2011). IKAP/Elp1 involvement in cytoskeleton regulation and implication for familial dysautonomia. Hum Mol Genet, 20(8), 1585-1594. Chen, C. New research directions in DNA repair. Chen, C., Huang, B., Eliasson, M., Ryden, P., & Bystrom, A. S. (2011). Elongator complex influences telomeric gene silencing and DNA damage response by its role in wobble uridine tRNA modification. PLoS Genet, 7(9), e1002258. Chen, C., Tuck, S., & Bystrom, A. S. (2009). Defects in tRNA modification associated with neurological and developmental dysfunctions in Caenorhabditis elegans elongator mutants. PLoS Genet, 5(7), e1000561. Chen, D., Toone, W. M., Mata, J., Lyne, R., Burns, G., Kivinen, K., Brazma, A., Jones, N., & Bahler, J. (2003). Global transcriptional responses of fission yeast to environmental stress. Mol Biol Cell, 14(1), 214-229. Chen, D., Wilkinson, C. R., Watt, S., Penkett, C. J., Toone, W. M., Jones, N., & Bahler, J. (2008). Multiple pathways differentially regulate global oxidative stress responses in fission yeast. Mol Biol Cell, 19(1), 308-317. 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. Mol Cell Biol, 29(3), 736-744. Chia, G., Agudo, J., Treff, N., Sauer, M. V., Billing, D., Brown, B. D., Baer, R., & Egli, D. (2017). Genomic instability during reprogramming by nuclear transfer is DNA replication dependent. Nat Cell Biol, 19(4), 282-291. Chroscinski, D., Sampey, D., Hewitt, A., & Reproducibility Project: Cancer, B. (2014). Registered report: Melanoma genome sequencing reveals frequent PREX2 mutations. Elife, 3 Ciccia, A., & Elledge, S. J. (2010). The DNA damage response: making it safe to play with knives. Mol Cell, 40(2), 179-204. Cimprich, K. A., & Cortez, D. (2008). ATR: an essential regulator of genome integrity. Nat Rev Mol Cell Biol, 9(8), 616-627. Cohen, L., Henzel, W. J., & Baeuerle, P. A. (1998). IKAP is a scaffold protein of the IkappaB kinase complex. Nature, 395(6699), 292-296. Creppe, C., Malinouskaya, L., Volvert, M. L., Gillard, M., Close, P., Malaise, O., Laguesse, S., Cornez, I., Rahmouni, S., Ormenese, S., Belachew, S., Malgrange, B., Chapelle, J. P., Siebenlist, U., Moonen, G., Chariot, A., & Nguyen, L. (2009). Elongator controls the migration and differentiation of cortical neurons through acetylation of alpha-tubulin. Cell, 136(3), 551-564. Cui, Y., & Paules, R. S. (2010). Use of transcriptomics in understanding mechanisms of drug-induced toxicity. Pharmacogenomics, 11(4), 573-585. Cunningham, F. H., Fiebelkorn, S., Johnson, M., & Meredith, C. (2011). A novel application of the Margin of Exposure approach: segregation of tobacco smoke toxicants. Food Chem Toxicol, 49(11), 2921-2933. Cuozzo, C., Porcellini, A., Angrisano, T., Morano, A., Lee, B., Di Pardo, A., Messina, S., Iuliano, R., Fusco, A., Santillo, M. R., Muller, M. T., Chiariotti, L., Gottesman, M. E., & Avvedimento, E. V. (2007). DNA damage, homology-directed repair, and DNA methylation. PLoS Genet, 3(7), e110. Cuozzo, C., Porcellini, A., Angrisano, T., Morano, A., Lee, B., Pardo, A. D., Messina, S., Iuliano, R., Fusco, A., Santillo, M. R., Muller, M. T., Chiariotti, L., Gottesman, M. E., & Avvedimento, E. V. (2017). Correction: DNA Damage, Homology-Directed Repair, and DNA Methylation. PLoS Genet, 13(2), e1006605. d'Adda di Fagagna, F. (2014). A direct role for small non-coding RNAs in DNA damage response. Trends Cell Biol, 24(3), 171-178. Daley, J. M., Palmbos, P. L., Wu, D., & Wilson, T. E. (2005). Nonhomologous end joining in yeast. Annu Rev Genet, 39, 431-451. Dauden, M. I., Kosinski, J., Kolaj-Robin, O., Desfosses, A., Ori, A., Faux, C., Hoffmann, N. A., Onuma, O. F., Breunig, K. D., Beck, M., Sachse, C., Seraphin, B., Glatt, S., & Muller, C. W. (2016). Architecture of the yeast Elongator complex. EMBO Rep Degos, L. (2001). John Hughes Bennett, Rudolph Virchow... and Alfred Donne: the first description of leukemia. Hematol J, 2(1), 1. Ducray, C., Pommier, J. P., Martins, L., Boussin, F. D., & Sabatier, L. (1999). Telomere dynamics, end-to-end fusions and telomerase activation during the human fibroblast immortalization process. Oncogene, 18(29), 4211-4223. Esberg, A., Huang, B., Johansson, M. J., & Bystrom, A. S. (2006). Elevated levels of two tRNA species bypass the requirement for elongator complex in transcription and exocytosis. Mol Cell, 24(1), 139-148. Facista, A., Nguyen, H., Lewis, C., Prasad, A. R., Ramsey, L., Zaitlin, B., Nfonsam, V., Krouse, R. S., Bernstein, H., Payne, C. M., Stern, S., Oatman, N., Banerjee, B., & Bernstein, C. (2012). Deficient expression of DNA repair enzymes in early progression to sporadic colon cancer. Genome Integr, 3(1), 3. Falzon, M., Fewell, J. W., & Kuff, E. L. (1993). EBP-80, a transcription factor closely resembling the human autoantigen Ku, recognizes single- to double-strand transitions in DNA. J Biol Chem, 268(14), 10546-10552. Fernandez-Vazquez, J., Vargas-Perez, I., Sanso, M., Buhne, K., Carmona, M., Paulo, E., Hermand, D., Rodriguez-Gabriel, M., Ayte, J., Leidel, S., & Hidalgo, E. (2013). Modification of tRNA(UUU)(Lys) by Elongator Is Essential for Efficient Translation of Stress mRNAs. Plos Genetics, 9(7) Fichtner, L., Jablonowski, D., Schierhorn, A., Kitamoto, H. K., Stark, M. J. R., & Schaffrath, R. (2003). Elongator's toxin-target (TOT) function is nuclear localization sequence dependent and suppressed by post-translational modification. Molecular Microbiology, 49(5), 1297-1307. Fishel, R., Lescoe, M. K., Rao, M. R., Copeland, N. G., Jenkins, N. A., Garber, J., Kane, M., & Kolodner, R. (1994). The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell, 77(1), 1 p following 166. Flanagan, J. M., Healey, S., Young, J., Whitehall, V., Trott, D. A., Newbold, R. F., & Chenevix-Trench, G. (2004). Mapping of a candidate colorectal cancer tumor-suppressor gene to a 900-kilobase region on the short arm of chromosome 8. Genes Chromosomes Cancer, 40(3), 247-260. Foray, N., Charvet, A. M., Duchemin, D., Favaudon, V., & Lavalette, D. (2005). The repair rate of radiation-induced DNA damage: a stochastic interpretation based on the gamma function. J Theor Biol, 236(4), 448-458. Francia, S. (2015). Non-Coding RNA: Sequence-Specific Guide for Chromatin Modification and DNA Damage Signaling. Front Genet, 6, 320. Frattini, A., Fabbri, M., Valli, R., De Paoli, E., Montalbano, G., Gribaldo, L., Pasquali, F., & Maserati, E. (2015). High variability of genomic instability and gene expression profiling in different HeLa clones. Sci Rep, 5, 15377. Frohloff, F., Fichtner, L., Jablonowski, D., Breunig, K. D., & Schaffrath, R. (2001). Saccharomyces cerevisiae Elongator mutations confer resistance to the Kluyveromyces lactis zymocin. EMBO J, 20(8), 1993-2003. Garfield, A. S. (2010). Derivation of primary mouse embryonic fibroblast (PMEF) cultures. Methods Mol Biol, 633, 19-27. German, J. (1969). Bloom's syndrome. I. Genetical and clinical observations in the first twenty-seven patients. Am J Hum Genet, 21(2), 196-227. Glatt, S., Letoquart, J., Faux, C., Taylor, N. M., Seraphin, B., & Muller, C. W. (2012). The Elongator subcomplex Elp456 is a hexameric RecA-like ATPase. Nat Struct Mol Biol, 19(3), 314-320. Glatt, S., & Muller, C. W. (2013). Structural insights into Elongator function. Current Opinion in Structural Biology, 23(2), 235-242. Glatt, S., Seraphin, B., & Muller, C. W. (2012). Elongator: transcriptional or translational regulator? Transcription, 3(6), 273-276. Glatt, S., Zabel, R., Kolaj-Robin, O., Onuma, O. F., Baudin, F., Graziadei, A., Taverniti, V., Lin, T. Y., Baymann, F., Seraphin, B., Breunig, K. D., & Muller, C. W. (2016). Structural basis for tRNA modification by Elp3 from Dehalococcoides mccartyi. Nat Struct Mol Biol, 23(9), 794-802. Gonzalez, F., Georgieva, D., Vanoli, F., Shi, Z. D., Stadtfeld, M., Ludwig, T., Jasin, M., & Huangfu, D. (2013). Homologous recombination DNA repair genes play a critical role in reprogramming to a pluripotent state. Cell Rep, 3(3), 651-660. Gottschalk, A. J., Timinszky, G., Kong, S. E., Jin, J. J., Cai, Y., Swanson, S. K., Washburn, M. P., Florens, L., Ladurner, A. G., Conaway, J. W., & Conaway, R. C. (2009). Poly(ADP-ribosyl)ation directs recruitment and activation of an ATP-dependent chromatin remodeler. Proceedings of the National Academy of Sciences of the United States of America, 106(33), 13770-13774. Halazonetis, T. D., Gorgoulis, V. G., & Bartek, J. (2008). An oncogene-induced DNA damage model for cancer development. Science, 319(5868), 1352-1355. Halford, S., Rowan, A., Sawyer, E., Talbot, I., & Tomlinson, I. (2005). O(6)-methylguanine methyltransferase in colorectal cancers: detection of mutations, loss of expression, and weak association with G:C>A:T transitions. Gut, 54(6), 797-802. Handa, O., Naito, Y., & Yoshikawa, T. (2011). Redox biology and gastric carcinogenesis: the role of Helicobacter pylori. Redox Rep, 16(1), 1-7. Harper, J. W., & Elledge, S. J. (2007). The DNA damage response: ten years after. Mol Cell, 28(5), 739-745. Harrison, J. C., & Haber, J. E. (2006). Surviving the breakup: the DNA damage checkpoint. Annu Rev Genet, 40, 209-235. Hawkes, N. A., Otero, G., Winkler, G. S., Marshall, N., Dahmus, M. E., Krappmann, D., Scheidereit, C., Thomas, C. L., Schiavo, G., Erdjument-Bromage, H., Tempst, P., & Svejstrup, J. Q. (2002). Purification and characterization of the human elongator complex. J Biol Chem, 277(4), 3047-3052. Hayflick, L. (1965). The Limited in Vitro Lifetime of Human Diploid Cell Strains. Exp Cell Res, 37, 614-636. Hegan, D. C., Narayanan, L., Jirik, F. R., Edelmann, W., Liskay, R. M., & Glazer, P. M. (2006). Differing patterns of genetic instability in mice deficient in the mismatch repair genes Pms2, Mlh1, Msh2, Msh3 and Msh6. Carcinogenesis, 27(12), 2402-2408. Hirao, A., Kong, Y. Y., Matsuoka, S., Wakeham, A., Ruland, J., Yoshida, H., Liu, D., Elledge, S. J., & Mak, T. W. (2000). DNA damage-induced activation of p53 by the checkpoint kinase Chk2. Science, 287(5459), 1824-1827. Hoekstra, M. F., Liskay, R. M., Ou, A. C., DeMaggio, A. J., Burbee, D. G., & Heffron, F. (1991). HRR25, a putative protein kinase from budding yeast: association with repair of damaged DNA. Science, 253(5023), 1031-1034. Hollander, M. C., Sheikh, M. S., Bulavin, D. V., Lundgren, K., Augeri-Henmueller, L., Shehee, R., Molinaro, T. A., Kim, K. E., Tolosa, E., Ashwell, J. D., Rosenberg, M. P., Zhan, Q., Fernandez-Salguero, P. M., Morgan, W. F., Deng, C. X., & Fornace, A. J., Jr. (1999). Genomic instability in Gadd45a-deficient mice. Nat Genet, 23(2), 176-184. Holmberg, C., Katz, S., Lerdrup, M., Herdegen, T., Jaattela, M., Aronheim, A., & Kallunki, T. (2002). A novel specific role for I kappa B kinase complex-associated protein in cytosolic stress signaling. Journal of Biological Chemistry, 277(35), 31918-31928. Horrigan, S. K., Courville, P., Sampey, D., Zhou, F., Cai, S., & Reproducibility Project: Cancer, B. (2017). Replication Study: Melanoma genome sequencing reveals frequent PREX2 mutations. Elife, 6 Hou, Y. M., Gamper, H., & Yang, W. (2015). Post-transcriptional modifications to tRNA--a response to the genetic code degeneracy. RNA, 21(4), 642-644. Howerton, K., Schlaepfer, D. D., & Ilic, D. (2008). Establishment of cell lines from mouse embryos with early embryonic lethality. Cell Commun Adhes, 15(4), 379-383. Huang, B., Johansson, M. J., & Bystrom, A. S. (2005). An early step in wobble uridine tRNA modification requires the Elongator complex. RNA, 11(4), 424-436. Huang, X., & Darzynkiewicz, Z. (2006). Cytometric assessment of histone H2AX phosphorylation: a reporter of DNA damage. Methods Mol Biol, 314, 73-80. Iyer, R. R., Pluciennik, A., Burdett, V., & Modrich, P. L. (2006). DNA mismatch repair: functions and mechanisms. Chem Rev, 106(2), 302-323. Jacobs, P. A., Browne, C., Gregson, N., Joyce, C., & White, H. (1992). Estimates of the Frequency of Chromosome-Abnormalities Detectable in Unselected Newborns Using Moderate Levels of Banding. Journal of Medical Genetics, 29(2), 103-108. Johansen, L. D., Naumanen, T., Knudsen, A., Westerlund, N., Gromova, I., Junttila, M., Nielsen, C., Bottzauw, T., Tolkovsky, A., Westermarck, J., Coffey, E. T., Jaattela, M., & Kallunki, T. (2008). IKAP localizes to membrane ruffles with filamin A and regulates actin cytoskeleton organization and cell migration. J Cell Sci, 121(Pt 6), 854-864. Kadaja, M., Isok-Paas, H., Laos, T., Ustav, E., & Ustav, M. (2009). Mechanism of genomic instability in cells infected with the high-risk human papillomaviruses. PLoS Pathog, 5(4), e1000397. Kalhor, H. R., & Clarke, S. (2003). Novel methyltransferase for modified uridine residues at the wobble position of tRNA. Molecular and Cellular Biology, 23(24), 9283-9292. Kampen, K. R. (2012). The discovery and early understanding of leukemia. Leukemia Research, 36(1), 6-13. Kanavy, H. E., & Gerstenblith, M. R. (2011). Ultraviolet radiation and melanoma. Semin Cutan Med Surg, 30(4), 222-228. Karlsborn, T., Tukenmez, H., Mahmud, A. K., Xu, F., Xu, H., & Bystrom, A. S. (2014). Elongator, a conserved complex required for wobble uridine modifications in eukaryotes. RNA Biol, 11(12), 1519-1528. Kastan, M. B. (2008). DNA damage responses: mechanisms and roles in human disease: 2007 G.H.A. Clowes Memorial Award Lecture. Mol Cancer Res, 6(4), 517-524. Kastan, M. B., & Bartek, J. (2004). Cell-cycle checkpoints and cancer. Nature, 432(7015), 316-323. Katsurano, M., Niwa, T., Yasui, Y., Shigematsu, Y., Yamashita, S., Takeshima, H., Lee, M. S., Kim, Y. J., Tanaka, T., & Ushijima, T. (2012). Early-stage formation of an epigenetic field defect in a mouse colitis model, and non-essential roles of T- and B-cells in DNA methylation induction. Oncogene, 31(3), 342-351. Kennedy, R. D., & D'Andrea, A. D. (2006). DNA repair pathways in clinical practice: lessons from pediatric cancer susceptibility syndromes. J Clin Oncol, 24(23), 3799-3808. Kim, J. H., Lane, W. S., & Reinberg, D. (2002). Human Elongator facilitates RNA polymerase II transcription through chromatin. Proceedings of the National Academy of Sciences of the United States of America, 99(3), 1241-1246. Kinzler, K. W., & Vogelstein, B. (1997). Cancer-susceptibility genes. Gatekeepers and caretakers. Nature, 386(6627), 761, 763. Krappmann, D., Hatada, E. N., Tegethoff, S., Li, J., Klippel, A., Giese, K., Baeuerle, P. A., & Scheidereit, C. (2000). The I kappa B kinase (IKK) complex is tripartite and contains IKK gamma but not IKAP as a regular component. Journal of Biological Chemistry, 275(38), 29779-29787. Krogh, B. O., & Symington, L. S. (2004). Recombination proteins in yeast. Annu Rev Genet, 38, 233-271. Larrea, A. A., Lujan, S. A., & Kunkel, T. A. (2010). SnapShot: DNA mismatch repair. Cell, 141(4), 730 e731. Leach, F. S., Nicolaides, N. C., Papadopoulos, N., Liu, B., Jen, J., Parsons, R., Peltomaki, P., Sistonen, P., Aaltonen, L. A., Nystrom-Lahti, M., & et al. (1993). Mutations of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell, 75(6), 1215-1225. Lee, C., & Goldberg, J. (2010). Structure of Coatomer Cage Proteins and the Relationship among COPI, COPII, and Clathrin Vesicle Coats. Cell, 142(1), 123-132. Lefler, S., Cohen, M. A., Kantor, G., Cheishvili, D., Even, A., Birger, A., Turetsky, T., Gil, Y., Even-Ram, S., Aizenman, E., Bashir, N., Maayan, C., Razin, A., Reubinoff, B. E., & Weil, M. (2015). Familial Dysautonomia (FD) Human Embryonic Stem Cell Derived PNS Neurons Reveal that Synaptic Vesicular and Neuronal Transport Genes Are Directly or Indirectly Affected by IKBKAP Downregulation. PLoS One, 10(10), e0138807. Lehavi, O., Aizenstein, O., Bercovich, D., Pavzner, D., Shomrat, R., Orr-Urtreger, A., & Yaron, Y. (2003). Screening for familial dysautonomia in Israel: evidence for higher carrier rate among Polish Ashkenazi Jews. Genet Test, 7(2), 139-142. Li, Q., Fazly, A. M., 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. Lieber, M. R. (2008). The mechanism of human nonhomologous DNA end joining. J Biol Chem, 283(1), 1-5. Lieber, M. R. (2010). The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annu Rev Biochem, 79, 181-211. Lin, F. J., Shen, L., Jang, C. W., Falnes, P. O., & Zhang, Y. (2013). Ikbkap/Elp1 deficiency causes male infertility by disrupting meiotic progression. PLoS Genet, 9(5), e1003516. Lindahl, T. (1993). Instability and Decay of the Primary Structure of DNA. Nature, 362(6422), 709-715. Lodish, H. F. (2004). Molecular cell biology (5th ed.). New York: W.H. Freeman and Co. Loeb, L. A. (1991). Mutator phenotype may be required for multistage carcinogenesis. Cancer Res, 51(12), 3075-3079. Lyubimov, A. Y., Strycharska, M., & Berger, J. M. (2011). The nuts and bolts of ring-translocase structure and mechanism. Curr Opin Struct Biol, 21(2), 240-248. Malkin, D. (2011). Li-fraumeni syndrome. Genes Cancer, 2(4), 475-484. Mao, J. H., Perez-Losada, J., Wu, D., Delrosario, R., Tsunematsu, R., Nakayama, K. I., Brown, K., Bryson, S., & Balmain, A. (2004). Fbxw7/Cdc4 is a p53-dependent, haploinsufficient tumour suppressor gene. Nature, 432(7018), 775-779. Marcelain, K., Armisen, R., Aguirre, A., Ueki, N., Toro, J., Colmenares, C., & Hayman, M. J. (2012). Chromosomal instability in mouse embryonic fibroblasts null for the transcriptional co-repressor Ski. J Cell Physiol, 227(1), 278-287. Marmorstein, R. (2001). Structure of histone acetyltransferases. J Mol Biol, 311(3), 433-444. Mehlgarten, C., Jablonowski, D., Breunig, K. D., Stark, M. J., & Schaffrath, R. (2009). Elongator function depends on antagonistic regulation by casein kinase Hrr25 and protein phosphatase Sit4. Mol Microbiol, 73(5), 869-881. Mehlgarten, C., Jablonowski, D., Wrackmeyer, U., Tschitschmann, S., Sondermann, D., Jager, G., Gong, Z., Bystrom, A. S., Schaffrath, R., & Breunig, K. D. (2010). Elongator function in tRNA wobble uridine modification is conserved between yeast and plants. Mol Microbiol, 76(5), 1082-1094. Miskiewicz, K., Jose, L. E., Bento-Abreu, A., Fislage, M., Taes, I., Kasprowicz, J., Swerts, J., Sigrist, S., Versees, W., Robberecht, W., & Verstreken, P. (2011). ELP3 controls active zone morphology by acetylating the ELKS family member Bruchpilot. Neuron, 72(5), 776-788. Nakai, Y., Nakai, M., & Hayashi, H. (2008). Thio-modification of yeast cytosolic tRNA requires a ubiquitin-related system that resembles bacterial sulfur transfer systems. J Biol Chem, 283(41), 27469-27476. Nakatogawa, H. (2015). Hrr25: an emerging major player in selective autophagy regulation in Saccharomyces cerevisiae. Autophagy, 11(2), 432-433. Narayanan, L., Fritzell, J. A., Baker, S. M., Liskay, R. M., & Glazer, P. M. (1997). Elevated levels of mutation in multiple tissues of mice deficient in the DNA mismatch repair gene Pms2. Proc Natl Acad Sci U S A, 94(7), 3122-3127. Negrini, S., Gorgoulis, V. G., & Halazonetis, T. D. (2010). Genomic instability--an evolving hallmark of cancer. Nat Rev Mol Cell Biol, 11(3), 220-228. Nick McElhinny, S. A., Snowden, C. M., McCarville, J., & Ramsden, D. A. (2000). Ku recruits the XRCC4-ligase IV complex to DNA ends. Mol Cell Biol, 20(9), 2996-3003. Nowak, M. A., Komarova, N. L., Sengupta, A., Jallepalli, P. V., Shih Ie, M., Vogelstein, B., & Lengauer, C. (2002). The role of chromosomal instability in tumor initiation. Proc Natl Acad Sci U S A, 99(25), 16226-16231. Nowell, P. C. (1976). The clonal evolution of tumor cell populations. Science, 194(4260), 23-28. O'Hagan, H. M., Mohammad, H. P., & Baylin, S. B. (2008). Double Strand Breaks Can Initiate Gene Silencing and SIRT1-Dependent Onset of DNA Methylation in an Exogenous Promoter CpG Island. Plos Genetics, 4(8) Odes, E. J., Randolph-Quinney, P. S., Steyn, M., Throckmorton, Z., Smilg, J. S., Zipfel, B., Augustine, T. N., de Beer, F., Hoffman, J. W., Franklin, R. D., & Berger, L. R. (2016). Earliest hominin cancer: 1.7-million-year-old osteosarcoma from Swartkrans Cave, South Africa. South African Journal of Science, 112(7-8), 100-104. Okada, Y., Yamagata, K., Hong, K., Wakayama, T., & Zhang, Y. (2010). A role for the elongator complex in zygotic paternal genome demethylation. Nature, 463(7280), 554-558. Olive, P. L., & Banath, J. P. (2006). The comet assay: a method to measure DNA damage in individual cells. Nat Protoc, 1(1), 23-29. Otero, G., Fellows, J., Li, Y., de Bizemont, T., Dirac, A. M., Gustafsson, C. M., Erdjument-Bromage, H., Tempst, P., & Svejstrup, J. Q. (1999). Elongator, a multisubunit component of a novel RNA polymerase II holoenzyme for transcriptional elongation. Mol Cell, 3(1), 109-118. Paddison, P. J., Caudy, A. A., Bernstein, E., Hannon, G. J., & Conklin, D. S. (2002). Short hairpin RNAs (shRNAs) induce sequence-specific silencing in mammalian cells. Genes Dev, 16(8), 948-958. Paraskevopoulou, C., Fairhurst, S. A., Lowe, D. J., Brick, P., & Onesti, S. (2006). The Elongator subunit Elp3 contains a Fe4S4 cluster and binds S-adenosylmethionine. Mol Microbiol, 59(3), 795-806. Passerini, V., Ozeri-Galai, E., de Pagter, M. S., Donnelly, N., Schmalbrock, S., Kloosterman, W. P., Kerem, B., & Storchova, Z. (2016). The presence of extra chromosomes leads to genomic instability. Nat Commun, 7, 10754. Petrakis, T. G., Wittschieben, B. O., & Svejstrup, J. Q. (2004). Molecular architecture, structure-function relationship, and importance of the Elp3 subunit for the RNA binding of holo-elongator. J Biol Chem, 279(31), 32087-32092. Phizicky, E. M., & Alfonzo, J. D. (2010). Do all modifications benefit all tRNAs? FEBS Lett, 584(2), 265-271. Piazza, A., Serero, A., Boule, J. B., Legoix-Ne, P., Lopes, J., & Nicolas, A. (2012). Stimulation of Gross Chromosomal Rearrangements by the Human CEB1 and CEB25 Minisatellites in Saccharomyces cerevisiae Depends on G-Quadruplexes or Cdc13. Plos Genetics, 8(11) Potapova, T. A., Zhu, J., & Li, R. (2013). Aneuploidy and chromosomal instability: a vicious cycle driving cellular evolution and cancer genome chaos. Cancer Metastasis Rev, 32(3-4), 377-389. Qvist, P., Huertas, P., Jimeno, S., Nyegaard, M., Hassan, M. J., Jackson, S. P., & Borglum, A. D. (2011). CtIP Mutations Cause Seckel and Jawad Syndromes. PLoS Genet, 7(10), e1002310. Rahl, P. B., Chen, C. Z., & Collins, R. N. (2005). Elp1p, the yeast homolog of the FD disease syndrome protein, negatively regulates exocytosis independently of transcriptional elongation. Mol Cell, 17(6), 841-853. Reinhardt, H. C., & Schumacher, B. (2012). The p53 network: cellular and systemic DNA damage responses in aging and cancer. Trends Genet, 28(3), 128-136. Ripperger, T., Gadzicki, D., Meindl, A., & Schlegelberger, B. (2009). Breast cancer susceptibility: current knowledge and implications for genetic counselling. European Journal of Human Genetics, 17(6), 722-731. Roos, W. P., & Kaina, B. (2006). DNA damage-induced cell death by apoptosis. Trends Mol Med, 12(9), 440-450. Sadikovic, B., Al-Romaih, K., Squire, J. A., & Zielenska, M. (2008). Cause and consequences of genetic and epigenetic alterations in human cancer. Curr Genomics, 9(6), 394-408. Sanso, M., Vargas-Perez, I., Garcia, P., Ayte, J., & Hidalgo, E. (2011). Nuclear roles and regulation of chromatin structure by the stress-dependent MAP kinase Sty1 of Schizosaccharomyces pombe. Mol Microbiol, 82(3), 542-554. Sanso, M., Vargas-Perez, I., Quintales, L., Antequera, F., Ayte, J., & Hidalgo, E. (2011). Gcn5 facilitates Pol II progression, rather than recruitment to nucleosome-depleted stress promoters, in Schizosaccharomyces pombe. Nucleic Acids Res, 39(15), 6369-6379. Sartori, A. A., Lukas, C., Coates, J., Mistrik, M., Fu, S., Bartek, J., Baer, R., Lukas, J., & Jackson, S. P. (2007). Human CtIP promotes DNA end resection. Nature, 450(7169), 509-514. Seller, M. J., Fear, C., Kumar, A., & Mohammed, S. (2004). Trisomy 16 in a mid-trimester IVF foetus with multiple abnormalities. Clin Dysmorphol, 13(3), 187-189. Sen, S. (2000). Aneuploidy and cancer. Curr Opin Oncol, 12(1), 82-88. Sharma, V., & Misteli, T. (2013). Non-coding RNAs in DNA damage and repair. FEBS Lett, 587(13), 1832-1839. Shrivastav, M., De Haro, L. P., & Nickoloff, J. A. (2008). Regulation of DNA double-strand break repair pathway choice. Cell Res, 18(1), 134-147. Simon, R., & Roychowdhury, S. (2013). Implementing personalized cancer genomics in clinical trials. Nat Rev Drug Discov, 12(5), 358-369. Singh, N., Lorbeck, M. T., Zervos, A., Zimmerman, J., & Elefant, F. (2010). The histone acetyltransferase Elp3 plays in active role in the control of synaptic bouton expansion and sleep in Drosophila. J Neurochem, 115(2), 493-504. Singh, S. V., Srivastava, S. K., Choi, S., Lew, K. L., Antosiewicz, J., Xiao, D., Zeng, Y., Watkins, S. C., Johnson, C. S., Trump, D. L., Lee, Y. J., Xiao, H., & Herman-Antosiewicz, A. (2005). Sulforaphane-induced cell death in human prostate cancer cells is initiated by reactive oxygen species. J Biol Chem, 280(20), 19911-19924. Singhal, P. K., Sassi, S., Lan, L., Au, P., Halvorsen, S. C., Fukumura, D., Jain, R. K., & Seed, B. (2016). Mouse embryonic fibroblasts exhibit extensive developmental and phenotypic diversity. Proc Natl Acad Sci U S A, 113(1), 122-127. Slaugenhaupt, S. A., Blumenfeld, A., Gill, S. P., Leyne, M., Mull, J., Cuajungco, M. P., Liebert, C. B., Chadwick, B., Idelson, M., Re | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/67112 | - |
| dc.description.abstract | 基因組不穩定性通常在細胞複製或分裂時發生，起因於染色體損壞未被修復且不斷的累積，而基因組的不穩定性已知與許多癌症有關。生物體為將細胞內的遺傳物質準確傳遞到子代，染色體的損壞修復機制實為重要。Ikbkap 基因編碼 IKAP/Elp1 蛋白質，為延伸因子 (Elongator complex, Elp1-6) 蛋白的其中一個子單元，依據蛋白質結構分析 Elp1 之功能顯示，其結構為維持延伸因子蛋白之構型所必要。延伸因子最初被發現參與第二型RNA聚合酶轉譯作用，而後更被發現參與許多細胞內生理活動。延伸因子調控細胞之方式目前認為主要是透過組蛋白乙醯化 (Histone Acetylation) 或轉運核糖核酸修飾 (tRNA modification)。先前的研究顯示 Ikbkap 參與小鼠精細胞減數分裂時染色體的聯會、雙股 DNA 斷裂修復與重組。在 Ikbkap 缺失的小鼠睪丸組織中，與DNA修復相關的基因表現量下降，這些結果說明了Ikbkap 在精細胞中可能參與DNA損壞修復。為探討 Ikbkap 在體細胞中是否也參與基因組穩定性的維持，我們以基因剔除之方式觀察小鼠纖維母細胞(Mouse Embryonic Fibroblast, MEFs) 。我們發現在 MEF 細胞中缺乏 Ikbkap ，且經過輻射線照射過後細胞生長曲線下降、在彗星試驗中發現 Ikbkap 缺乏會影響 DNA雙股斷裂後的修復，在染色體分析實驗發現 Ikbkap 缺失相較於 Ikbpap 正常表現的組別，異常的染色體比例顯著增加、但 Ikbkap 缺失且給予照射輻射線後 24 小時並不會導致細胞死亡。故本篇研究認為 Ikbkap 基因影響 DNA 斷裂後的細胞存活，且與染色體修復有關。 此外，我們利用帶有綠螢光報導基因的 U-2 OS 細胞來探討 Ikbkap 是否參與 DNA 雙股斷裂修復，發現 Ikbkap 參與在染色體同源雙股斷裂的修復而不是在非同源性末端接合的修復。後續之研究將會著重於 Ikbkap 如何參與 DNA 修復與相關機制的探討。 | zh_TW |
| dc.description.abstract | Genomic instability refers to an increased tendency of alterations in the genome during cell cycle progression, and likely contributes to the development of many cancers. To faithfully transmit genetic information to the progeny, efficient DNA repair pathways are required for the maintenance of genomic stability. Ikbkap gene encodes IKAP/Elp1, which functions as a scaffold subunit of the Elongator complex (Elp1-6). The Elongator complex was initially described as an RNA polymerase II-associated transcription elongation factor, but it has been shown later to be involved in a variety of cellular functions through regulation of histone acetylation and tRNA modification. A previous study has shown that Ikbkap regulates meiotic synapsis, double strand break (DSB) repair and recombination during male meiotic progression. Downregulation of DNA repair-related genes was observed in Ikbkap deficient testes, suggesting that Ikbkap plays a crucial role in DNA damage response (DDR) in germ cells. To investigate whether Ikbkap maintains genomic stability in somatic cells, we deleted Ikbkap in mouse embryonic fibroblasts (MEFs). Comet assays show that Ikbkap-/- MEFs are hypersensitive to DNA damage, like -irradiation. Ikbkap-/- MEFs exhibited a proliferative impediment in response to -irradiation. In addition, a significant accumulation of chromosomal abnormalities, including breaks was observed in Ikbkap-/- MEFs compared to controls. Although apoptotic rate was unaffected in Ikbkap-/- MEFs one day post -irradiation, these data shows that IKAP function is essential for the ability to survive DNA damage, and implicating IKAP in repair in U-2 OS cells. Furthermore, we revealed that Ikbkap is required for DNA repair by homologous recombination (HR), but not non-homologous end joining (NHEJ) using U-2 OS cell lines harbouring a green fluorescent protein reporter for DSB repair. These finding define a function of Ikbkap in DNA repair. Further investigation will be focused on the underlying DNA repair mechanisms. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-17T01:20:16Z (GMT). No. of bitstreams: 1 ntu-106-R04b22062-1.pdf: 7945453 bytes, checksum: ee9bb72f13ff4ae85a2ae269e137bbbc (MD5) Previous issue date: 2017 | en |
| dc.description.tableofcontents | ACKNOWLEDGEMENT i
中文摘要 ii ABSTRACT iii Chapter 1 INTRODUCTION 1 1.1 The Tumor 1 1.1.1 The Cause of Tumor Cells 2 1.1.2 The Consequences of Cancer 3 1.1.3 The Role of Genomic Instability in Cancer 5 1.2 Genomic Instability 6 1.2.1 DNA Damage Response 8 1.2.2 DNA Repair 10 1.2.3 HR and NHEJ repair in DSB 11 1.2.4 The cause of impaired DNA repair 12 1.3 Elongator Complex Protein 13 1.3.1 The Structural Function of Elongator Complex 14 1.3.1.1 Elp1 15 1.3.1.2 Elp2 16 1.3.1.3 Elp3 17 1.3.1.4 Elp456 17 1.3.2 Elp1 Plays an Important Role in Neurongenesis and Neuron Disease 18 1.3.3 Elp1 Regulates Cell Programming and Meiosis further effect genomic instability 19 1.4 tRNA Modification and Post translation 19 1.4.1 The Mechanism of tRNA Modification 19 1.4.2 The Regulating Role of Elongator Complex Through tRNA modification 21 1.5 The Mouse Embryonic Fibroblast 23 1.5.1 The Advantage of Using MEFs 23 1.6 Hypothesis 25 1.6.1 Aim 1: Does Ikbkap / Elp1 deficiency associate with genomic instability? 25 1.6.2 Aim 2: Is Ikbkap/ Elp1 involved in DNA repair 28 Chapter 2 Material and Methods 33 2.1 Tissue isolation and genotyping 33 2.2 Immortalization of MEFs (iMEFs) 34 2.3 Generation of Ikbkap knockout iMEFs 35 2.4 Immunoblotting 36 2.5 Quantitative reverse transcription and real-time PCR 37 2.6 Cell viability assay 38 2.7 Metaphase chromosome spread 38 2.8 Comet assay 39 2.9 shRNA knockdown of Ikbkap in U-2 OS cells 40 2.10 Induction of DSB by transient expression of I-SceI endonuclease 40 2.11 DNA double strand break(DSB) repair analysis by flow cytometry 41 2.12 Immunoblotting of Elp1 and I-SceI protein in U-2 OS cells 41 2.13 Detection of apoptosis using annexin V and PI 42 2.14 Statistical analysis 43 Chapter 3 Results 44 3.1 Generation of conditional Ikbkap/Elp1 knockout in mouse embryonic fibroblasts (MEFs) 44 3.2 Deletion of Ikbkap/ Elp1 decreases cell viability in response to irradiation 45 3.3 Abnormal chromosome morphology was observed in Ikbkap /Elp1 deficient iMEFs 46 3.4 Deletion of Ikbkap / Elp1 Leads to Levels of DNA Damage upon irradiation 47 3.5 To generate Ikbkap knockdown cell in U-2 OS reporter system 48 3.6 Ikbkap/ Elp1 is mainly involved in homologous recombination repair 50 3.7 Deletion of Ikbkap / Elp1 does not promote apoptosis in early stage in iMEFs 51 Chapter 4 Discussion 64 4.1 The use of MEFs to investigate genomic instability 64 4.2 The use of immortalized MEFs (iMEFs) in the study 64 4.3 Compare the differences between inducible Cre knockout or Cre virus induced knockout in the study? 65 4.4 Deletion of Ikbkap caused embryonic death in mice, but not MEFs 66 4.5 No difference of comet tail moment in comet assay in Ikbkap deficiency? 67 4.6 The early apoptosis or late apoptosis in our apoptosis assay 68 4.7 The irradiation exposed cells with no significant difference in apoptosis 69 4.8 Future perspective 70 Chapter 5 Summary and Future Directions 72 Chapter 6 Bibliography 73 Chapter 7 Appendix 85 | |
| dc.language.iso | en | |
| dc.subject | 基因組不穩定性 | zh_TW |
| dc.subject | 輻射 | zh_TW |
| dc.subject | 同源重組DNA修復 | zh_TW |
| dc.subject | 染色體型態 | zh_TW |
| dc.subject | 細胞凋亡 | zh_TW |
| dc.subject | chromosome morphology | en |
| dc.subject | irradiation | en |
| dc.subject | genomic instability | en |
| dc.subject | apoptosis | en |
| dc.subject | homologous recombination DNA repair | en |
| dc.title | 探討Ikbkap/ Elp1 在基因組不穩定性中扮演的角色 | zh_TW |
| dc.title | Investigate the Role of Ikbkap/ Elp1 in Genomic Instability | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 105-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 冀宏源(Hung-Yuan Chi),黃青真(Ching-jang Huang),陳律佑(Liuh-Yow Chen),張茂山(Mau Sun Chang) | |
| dc.subject.keyword | 基因組不穩定性,輻射,同源重組DNA修復,染色體型態,細胞凋亡, | zh_TW |
| dc.subject.keyword | genomic instability,irradiation,homologous recombination DNA repair,chromosome morphology,apoptosis, | en |
| dc.relation.page | 85 | |
| dc.identifier.doi | 10.6342/NTU201702915 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2017-08-11 | |
| 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 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-106-1.pdf 未授權公開取用 | 7.76 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。