請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/49371完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 張鑫 | |
| dc.contributor.author | Yan-Shuo Liou | en |
| dc.contributor.author | 劉彥碩 | zh_TW |
| dc.date.accessioned | 2021-06-15T11:25:41Z | - |
| dc.date.available | 2021-08-26 | |
| dc.date.copyright | 2016-08-26 | |
| dc.date.issued | 2016 | |
| dc.date.submitted | 2016-08-18 | |
| dc.identifier.citation | Appel, N., et al. (2005). 'Mutational analysis of hepatitis C virus nonstructural protein 5A: potential role of differential phosphorylation in RNA replication and identification of a genetically flexible domain.' J Virol 79(5): 3187-3194.
Basile, G., et al. (2014). 'Checkpoint-dependent and independent roles of the Werner syndrome protein in preserving genome integrity in response to mild replication stress.' Nucleic Acids Res 42(20): 12628-12639. Baumann, P. and S. C. West (1998). 'Role of the human RAD51 protein in homologous recombination and double-stranded-break repair.' Trends Biochem Sci 23(7): 247-251. Bittar, C., et al. (2013). 'Hepatitis C virus NS2 protein inhibits DNA damage pathway by sequestering p53 to the cytoplasm.' PLoS One 8(4): e62581. Blight, K. J. (2011). 'Charged residues in hepatitis C virus NS4B are critical for multiple NS4B functions in RNA replication.' J Virol 85(16): 8158-8171. Bonkovsky, H. L. and S. Mehta (2001). 'Hepatitis C: a review and update.' J Am Acad Dermatol 44(2): 159-182. Bosch, F. X., et al. (2004). 'Primary liver cancer: worldwide incidence and trends.' Gastroenterology 127(5 Suppl 1): S5-s16. Caldecott, K. W. (2007). 'Mammalian single-strand break repair: mechanisms and links with chromatin.' DNA Repair (Amst) 6(4): 443-453. Chang, S. C., et al. (2000). 'Roles of the AX(4)GKS and arginine-rich motifs of hepatitis C virus RNA helicase in ATP- and viral RNA-binding activity.' J Virol 74(20): 9732-9737. Chang, S. C., et al. (1994). 'Nuclear localization signals in the core protein of hepatitis C virus.' Biochem Biophys Res Commun 205(2): 1284-1290. Cheng, W. H. and V. A. Bohr (2003). 'Diverse dealings of the Werner helicase/nuclease.' Sci Aging Knowledge Environ 2003(31): Pe22. Choo, Q. L., et al. (1989). 'Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome.' Science 244(4902): 359-362. Choo, Q. L., et al. (1989). 'Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome.' Science 244(4902): 359-362. Choo, Q. L., et al. (1991). 'Genetic organization and diversity of the hepatitis C virus.' Proc Natl Acad Sci U S A 88(6): 2451-2455. Dallaire, A., et al. (2012). 'Down regulation of miR-124 in both Werner syndrome DNA helicase mutant mice and mutant Caenorhabditis elegans wrn-1 reveals the importance of this microRNA in accelerated aging.' Aging (Albany NY) 4(9): 636-647. David, S. S., et al. (2007). 'Base-excision repair of oxidative DNA damage.' Nature 447(7147): 941-950. David, S. S. and S. D. Williams (1998). 'Chemistry of Glycosylases and Endonucleases Involved in Base-Excision Repair.' Chem Rev 98(3): 1221-1262. Demple, B. and J. S. Sung (2005). 'Molecular and biological roles of Ape1 protein in mammalian base excision repair.' DNA Repair (Amst) 4(12): 1442-1449. Farazi, P. A. and R. A. DePinho (2006). 'Hepatocellular carcinoma pathogenesis: from genes to environment.' Nat Rev Cancer 6(9): 674-687. Friebe, P. and R. Bartenschlager (2002). 'Genetic analysis of sequences in the 3' nontranslated region of hepatitis C virus that are important for RNA replication.' J Virol 76(11): 5326-5338. Gale, M., Jr., et al. (1998). 'Control of PKR protein kinase by hepatitis C virus nonstructural 5A protein: molecular mechanisms of kinase regulation.' Mol Cell Biol 18(9): 5208-5218. Ghosal, G. and J. Chen (2013). 'DNA damage tolerance: a double-edged sword guarding the genome.' Transl Cancer Res 2(3): 107-129. Ghosal, G. and J. Chen (2013). 'DNA damage tolerance: a double-edged sword guarding the genome.' Transl Cancer Res 2(3): 107-129. Goffard, A., et al. (2005). 'Role of N-linked glycans in the functions of hepatitis C virus envelope glycoproteins.' J Virol 79(13): 8400-8409. Gogela, N. A., et al. (2015). 'Enhancing our understanding of current therapies for hepatitis C virus (HCV).' Curr HIV/AIDS Rep 12(1): 68-78. Graf, N., et al. (2011). 'Role of endonucleases XPF and XPG in nucleotide excision repair of platinated DNA and cisplatin/oxaliplatin cytotoxicity.' Chembiochem 12(7): 1115-1123. Grakoui, A., et al. (1993). 'Characterization of the hepatitis C virus-encoded serine proteinase: determination of proteinase-dependent polyprotein cleavage sites.' J Virol 67(5): 2832-2843. Gu, L., et al. (1998). 'ATP-dependent interaction of human mismatch repair proteins and dual role of PCNA in mismatch repair.' Nucleic Acids Res 26(5): 1173-1178. Han, J. H., et al. (1991). 'Characterization of the terminal regions of hepatitis C viral RNA: identification of conserved sequences in the 5' untranslated region and poly(A) tails at the 3' end.' Proc Natl Acad Sci U S A 88(5): 1711-1715. Huyen, Y., et al. (2004). 'Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks.' Nature 432(7015): 406-411. Iizuka, N., et al. (2002). 'Comparison of gene expression profiles between hepatitis B virus- and hepatitis C virus-infected hepatocellular carcinoma by oligonucleotide microarray data on the basis of a supervised learning method.' Cancer Res 62(14): 3939-3944. Kou, Y. H., et al. (2007). 'Differential requirements of NS4A for internal NS3 cleavage and polyprotein processing of hepatitis C virus.' J Virol 81(15): 7999-8008. Kumagai, A., et al. (2006). 'TopBP1 activates the ATR-ATRIP complex.' Cell 124(5): 943-955. Kusumoto, R., et al. (2008). 'Werner protein cooperates with the XRCC4-DNA ligase IV complex in end-processing.' Biochemistry 47(28): 7548-7556. Lai, C. K., et al. (2008). 'Hepatitis C virus NS3/4A protein interacts with ATM, impairs DNA repair and enhances sensitivity to ionizing radiation.' Virology 370(2): 295-309. Leber, R., et al. (1998). 'The XRCC4 gene product is a target for and interacts with the DNA-dependent protein kinase.' J Biol Chem 273(3): 1794-1801. Lee, J. H. and T. T. Paull (2005). 'ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex.' Science 308(5721): 551-554. Lerat, H., et al. (2002). 'Steatosis and liver cancer in transgenic mice expressing the structural and nonstructural proteins of hepatitis C virus.' Gastroenterology 122(2): 352-365. Lieber, M. R., et al. (2010). 'Nonhomologous DNA end joining (NHEJ) and chromosomal translocations in humans.' Subcell Biochem 50: 279-296. Lundin, M., et al. (2003). 'Topology of the membrane-associated hepatitis C virus protein NS4B.' J Virol 77(9): 5428-5438. Machida, K., et al. (2006). 'Hepatitis C virus triggers mitochondrial permeability transition with production of reactive oxygen species, leading to DNA damage and STAT3 activation.' J Virol 80(14): 7199-7207. Machida, K., et al. (2006). 'Hepatitis C virus triggers mitochondrial permeability transition with production of reactive oxygen species, leading to DNA damage and STAT3 activation.' J Virol 80(14): 7199-7207. Machida, K., et al. (2004). 'Hepatitis C virus infection activates the immunologic (type II) isoform of nitric oxide synthase and thereby enhances DNA damage and mutations of cellular genes.' J Virol 78(16): 8835-8843. Machida, K., et al. (2010). 'Hepatitis C virus inhibits DNA damage repair through reactive oxygen and nitrogen species and by interfering with the ATM-NBS1/Mre11/Rad50 DNA repair pathway in monocytes and hepatocytes.' J Immunol 185(11): 6985-6998. Matsumoto, Y., et al. (2000). 'Cleavage and phosphorylation of XRCC4 protein induced by X-irradiation.' FEBS Lett 478(1-2): 67-71. McCulloch, S. D., et al. (2003). 'Bi-directional processing of DNA loops by mismatch repair-dependent and -independent pathways in human cells.' J Biol Chem 278(6): 3891-3896. Moriya, K., et al. (1998). 'The core protein of hepatitis C virus induces hepatocellular carcinoma in transgenic mice.' Nat Med 4(9): 1065-1067. Moser, J., et al. (2007). 'Sealing of chromosomal DNA nicks during nucleotide excision repair requires XRCC1 and DNA ligase III alpha in a cell-cycle-specific manner.' Mol Cell 27(2): 311-323. Niederau, C., et al. (1998). 'Prognosis of chronic hepatitis C: results of a large, prospective cohort study.' Hepatology 28(6): 1687-1695. Opresko, P. L. (2008). 'Telomere ResQue and preservation--roles for the Werner syndrome protein and other RecQ helicases.' Mech Ageing Dev 129(1-2): 79-90. Pawlotsky, J. M. (2003). 'Mechanisms of antiviral treatment efficacy and failure in chronic hepatitis C.' Antiviral Res 59(1): 1-11. Pileri, P., et al. (1998). 'Binding of hepatitis C virus to CD81.' Science 282(5390): 938-941. Reed, K. E. and C. M. Rice (1999). 'Identification of the major phosphorylation site of the hepatitis C virus H strain NS5A protein as serine 2321.' J Biol Chem 274(39): 28011-28018. Ross-Thriepland, D., et al. (2015). 'Serine phosphorylation of the hepatitis C virus NS5A protein controls the establishment of replication complexes.' J Virol 89(6): 3123-3135. Sakamuro, D., et al. (1995). 'Hepatitis C virus nonstructural protein NS3 transforms NIH 3T3 cells.' J Virol 69(6): 3893-3896. Santolini, E., et al. (1994). 'Biosynthesis and biochemical properties of the hepatitis C virus core protein.' J Virol 68(6): 3631-3641. Scarselli, E., et al. (2002). 'The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus.' Embo j 21(19): 5017-5025. Shinagawa, H. and H. Iwasaki (1996). 'Processing the holliday junction in homologous recombination.' Trends Biochem Sci 21(3): 107-111. Simmonds, P. (2004). 'Genetic diversity and evolution of hepatitis C virus--15 years on.' J Gen Virol 85(Pt 11): 3173-3188. Steinmann, E., et al. (2007). 'Hepatitis C virus p7 protein is crucial for assembly and release of infectious virions.' PLoS Pathog 3(7): e103. Stempniak, M., et al. (1997). 'The NS3 proteinase domain of hepatitis C virus is a zinc-containing enzyme.' J Virol 71(4): 2881-2886. Stewart, G. S., et al. (2003). 'MDC1 is a mediator of the mammalian DNA damage checkpoint.' Nature 421(6926): 961-966. Sturzenegger, A., et al. (2014). 'DNA2 cooperates with the WRN and BLM RecQ helicases to mediate long-range DNA end resection in human cells.' J Biol Chem 289(39): 27314-27326. Suwa, A., et al. (1994). 'DNA-dependent protein kinase (Ku protein-p350 complex) assembles on double-stranded DNA.' Proc Natl Acad Sci U S A 91(15): 6904-6908. Tai, C. L., et al. (1996). 'The helicase activity associated with hepatitis C virus nonstructural protein 3 (NS3).' J Virol 70(12): 8477-8484. Tai, C. L., et al. (1996). 'The helicase activity associated with hepatitis C virus nonstructural protein 3 (NS3).' J Virol 70(12): 8477-8484. Tedbury, P. R. and M. Harris (2007). 'Characterisation of the role of zinc in the hepatitis C virus NS2/3 auto-cleavage and NS3 protease activities.' J Mol Biol 366(5): 1652-1660. Thorgeirsson, S. S. and J. W. Grisham (2002). 'Molecular pathogenesis of human hepatocellular carcinoma.' Nat Genet 31(4): 339-346. Watashi, K., et al. (2005). 'Cyclophilin B is a functional regulator of hepatitis C virus RNA polymerase.' Mol Cell 19(1): 111-122. Wolk, B., et al. (2000). 'Subcellular localization, stability, and trans-cleavage competence of the hepatitis C virus NS3-NS4A complex expressed in tetracycline-regulated cell lines.' J Virol 74(5): 2293-2304. Wu, S. C., et al. (2008). 'Hepatitis C virus NS5A protein down-regulates the expression of spindle gene Aspm through PKR-p38 signaling pathway.' J Biol Chem 283(43): 29396-29404. Zemel, R., et al. (2001). 'Cell transformation induced by hepatitis C virus NS3 serine protease.' J Viral Hepat 8(2): 96-102. Zou, L. and S. J. Elledge (2003). 'Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes.' Science 300(5625): 154 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/49371 | - |
| dc.description.abstract | C型肝炎病毒(Hepatitis C virus, HCV) 是臨床上肝臟疾病常見的病源之一，感染後會造成肝纖維化和肝細胞癌等症狀。病毒的nonstructural protein 3 (NS3)具有protease及RNA helicase的功能，而NS4A可以作為NS3 protease的cofactor。過去研究顯示NS3除了會造成DNA的損傷外，它還會干擾參與DNA修補作用蛋白質的功能。Werner syndrome protein (WRN)是RecQ DNA helicases family的一員，在過去的研究中發現它可做為helicase或者是exonuclease參與在DNA修復作用中。為了探討NS3是否會透過WRN影響DNA修復作用，本研究首先探討NS3是否影響WRN表現量，結果顯示NS3及NS3/4A都會使WRN的表現量下降，其中以NS3/4A的影響較顯著。又進一步探討NS3/4A的內部截切產物NS3(1-369)、NS3(1-402)、NS3(1-462)及NS3(327-631)是否會影響WRN的表現量，結果顯示NS3(1-462)造成WRN表現量下降的幅度最為明顯。接著以GST pull-down 實驗證實了NS3與WRN的交互作用。將NS3依照蛋白質功能與結構區分為protease domain、NTPase domain、RNA binding domain及helical domain，並利用GST pull-down分析時，發現以C-terminal的helical domain與WRN的交互作用最為顯著。由本研究的結果推測NS3使WRN表現量下降，而NS3對WRN的功能及其所參與的DNA修補作用有何影響有待進一步研究。 | zh_TW |
| dc.description.abstract | Hepatitis C virus (HCV) is one of the main pathogens that infect human liver. HCV infection often causes liver fibrosis and develops to hepatocellular carcinoma. The viral nonstructural protein (NS) 3 possesses protease and RNA helicase activities and NS4A functions as a cofactor of the NS3 protease. In previous studies, NS3 was demonstrated to induce DNA damage and interfere DNA repair of host cells. Nevertheless, the molecular mechanisms are not fully understood. Werner syndrome protein (WRN) is classified as a member of the RecQ DNA family. It possesses helicase and exonuclease activities and participates in DNA repair. To learn whether NS3 affects DNA repair though WRN, the effects of NS3 and NS3/4A on WRN expression were first examined in this study. The results showed decrease on WRN expression when NS3 or NS3/4A was present. In addition, NS3/4A internal cleavage product NS3(1-462) also caused a decrease on WRN expression. GST pull-down assay was then performed to examine the interaction between WRN and NS3. The results showed that WRN interacted with the full-length NS3 and its various subdomains, and more notably, the GST-NS3(402-631) and GST-NS3(462-631) with the C-terminal helical domain. Taken together, this study detected the interaction between WRN and HCV NS3 protein and the effect of NS3 on WRN expression. Whether NS3 affects WRN functions and influences DNA repair needs to be further investigated. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T11:25:41Z (GMT). No. of bitstreams: 1 ntu-105-R03445121-1.pdf: 2246495 bytes, checksum: 1f0bb1986b15071ad2d0ad95405a598c (MD5) Previous issue date: 2016 | en |
| dc.description.tableofcontents | 摘要 I
Abstract III 目錄 IV 緒論 1 一、 C型肝炎病毒 1 二、 肝細胞癌(Hepatocellular, HCC) 5 三、DNA損傷(DNA damage) 7 四、DNA修復(DNA repair) 8 五、C型肝炎病毒非結構性蛋白NS3 11 六、Werner syndrome protein (WRN) 12 研究目的 14 實驗材料 15 實驗方法 23 實驗結果 27 一、NS3及NS3/4A對WRN在細胞表現之影響 27 二、NS3及NS3蛋白質次區域對WRN在細胞表現之影響 27 三、NS3與WRN之間的交互作用 28 四、NS3蛋白次單元與WRN之間的交互作用 28 討論 30 一、NS3及NS3/4A表現時WRN表現量下降 30 二、NS3及NS3的蛋白次單元與WRN的交互作用 30 三、NS3及NS3/4A造成WRN表現量下降的可能原因 31 圖表 33 參考文獻 43 附錄 50 | |
| dc.language.iso | zh-TW | |
| dc.subject | WRN蛋白質 | zh_TW |
| dc.subject | C型肝炎病毒 | zh_TW |
| dc.subject | NS3蛋白質 | zh_TW |
| dc.subject | Hepatitis C virus | en |
| dc.subject | WRN | en |
| dc.subject | NS3 | en |
| dc.title | C型肝炎病毒非結構性蛋白質NS3與WRN的交互作用及對WRN表現量的影響 | zh_TW |
| dc.title | Hepatitis C virus nonstructural protein 3 interacts with WRN and affects its expression | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 104-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 董馨蓮,張永祺 | |
| dc.subject.keyword | C型肝炎病毒,NS3蛋白質,WRN蛋白質, | zh_TW |
| dc.subject.keyword | Hepatitis C virus,NS3,WRN, | en |
| dc.relation.page | 52 | |
| dc.identifier.doi | 10.6342/NTU201603278 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2016-08-18 | |
| 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-105-1.pdf 未授權公開取用 | 2.19 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。