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| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 張智芬 | |
| dc.contributor.author | Da-Wei Lin | en |
| dc.contributor.author | 林大為 | zh_TW |
| dc.date.accessioned | 2021-06-13T07:50:13Z | - |
| dc.date.available | 2005-08-26 | |
| dc.date.copyright | 2005-08-26 | |
| dc.date.issued | 2005 | |
| dc.date.submitted | 2005-07-25 | |
| dc.identifier.citation | Anderson S, Bankier AT, Barrell BG, de Bruijn MH, Coulson AR, Drouin J, Eperon IC, Nierlich DP, Roe BA, Sanger F, Schreier PH, Smith AJ, Staden R, Young IG. (1981). Sequence and organization of the human mitochondrial genome. Nature. 290, 457-65.
Attardi G, Schatz G. (1988). Biogenesis of mitochondria. Annu. Rev. Cell. Biol., 4, 289-333. Bestwick RK, Mathews CK. (1982). Unusual compartmentation of precursors for nuclear and mitochondrial DNA in mouse L cells. J. Biol. Chem. 257, 9305-8. Bogenhagen D, Clayton DA. (1977). Mouse L cell mitochondrial DNA molecules are selected randomly for replication throughout the cell cycle. Cell. 11, 719-27. Brundiers R, Lavie A, Veit T, Reinstein J, Schlichting I, Ostermann N, Goody RS, Konrad M. (1999). Modifying human thymidylate kinase to potentiate azidothymidine activation. J. Biol. Chem., 274, 35289-92. Claros MG, Vincens P. (1996).Computational method to predict mitochondrially imported proteins and their targeting sequences. Eur. J. Biochem., 241, 779-786. Cohn ZA. (1968). The structure and function of monocytes and macrophages. Adv Immunol. 9, 163-214. Copeland, WC, Wachsman JT, Johnson FM, and Penta JS. (2002). Mitochondrial DNA alterations in cancer. Cancer. Investig., 20, 557-569. Coppock DL, Pardee AB. (1987). Control of thymidine kinase mRNA during the cell cycle. Mol. Cell. Biol. 7, 2925-32. Demin OV, Kholodenko BN, Skulachev VP. (1998). A model of O2-generation in the complex III of the electron transport chain. Mol. Cell. Biochem. 184, 21-33. Dolce VV, Fiermonte G, Runswick MJ, Palmieri F, Walker JE. (2001). The human mitochondrial deoxynucleotide carrier and its role in toxicity of nucleoside antivirals. Proc. Natl. Acad. Sci. USA., 98, 2284-88. Elpeleg O. (2003). Inherited mitochondrial DNA depletion. Pediatr. Res., 54, 153-9. Fry DC, Kuby SA, Mildvan AS. (1986). ATP-binding site of adenylate kinase: mechanistic implications of its homology with ras-encoded p21, F1-ATPase, and other nucleotide-binding proteins. Proc. Natl. Acad. Sci. U S A., 83, 907-11. Genova ML, Ventura B, Giuliano G, Bovina C, Formiggini G, Parenti Castelli G, Lenaz G. (2001). The site of production of superoxide radical in mitochondrial Complex I is not a bound ubisemiquinone but presumably iron-sulfur cluster N2. FEBS. Lett. 21, 364-8. Herrero A, Barja G. (1997). Sites and mechanisms responsible for the low rate of free radical production of heart mitochondria in the long-lived pigeon. Mech. Ageing. Dev. 98, 95-111. Huang SH, Tang A, Drisco B, Zhang SQ, Seeger R, Li C. and Jong A. (1994) Human dTMP kinase: gene expression and enzymatic activity coinciding with cell cycle progression and cell growth. DNA Cell Biol., 5, 461-71. Hume DA, Yue X, Ross IL, Favot P, Lichanska A, Ostrowski MC. (1997). Regulation of CSF-1 receptor expression. Mol. Reprod. Dev., 46, 46-52. Johansson M and Karlsson A. (1996). Cloning and expression of human deoxyguanosine kinase cDNA. Proc. Natl. Acad. Sci U S A. 93, 7258-62. Johansson M and Karlsson A. (1997). Cloning of the cDNA and chromosome location of gene for Human Thymidine Kinase 2. J. Boil. Chem., 272, 8454-58. Jong AY and Campbell JL. (1984). Characterization of Saccharomyces cerevisiae thymidylate kinase, the CDC8 gene product. General properties, kinetic analysis, and subcellular localization. J. Biol. Chem.. 259, 14394-8. Kang D and Hamasaki N. (2005). Alterations of mitochondrial DNA in common diseases and disease states: aging, neurodegeneration, heart failure, diabetes, and cancer. Curr. Med. Chem. 12, 429-41. Ke PY and Chang ZF. (2003). Mitotic degradation of human thymidine kinase 1 is dependent on the Anaphase-Promoting Complex/Cyclosome-Cdh1 mediated pathway. Mol. Cell. Biol., 24, 514-26. Lee HC, Wei YH. (2004). Mitochondrial biogenesis and mitochondrial DNA maintenance of mammalian cells under oxidative stress. Int. J. Biochem. Cell. Biol. 37. 822-34. Lee LS, Cheng Y. (1977). Human thymidylate kinase. Purification, characterization, and kinetic behavior of the thymidylate kinase derived from chronic myelocytic leukemia. J. Biol. Chem., 252, 5686-91. Longley MJ, Nguyen D, Kunkel TA, Copeland WC. (2001). The fidelity of human DNA polymerase gamma with and without exonucleolytic proofreading and the p55 accessory subunit. J. Biol. Chem. 276, 38555-62. Milon L, Meyer P, Chiadmi M, Munier A, Johansson M, Karlsson A, Lascu I, Capeau J, Janin J, Lacombe ML. (2000). The human nm23-H4 gene product is a mitochondrial nucleoside diphosphate kinase. J. Biol. Chem., 275, 14264-72. Nishino I, Spinazzola A, Hirano M. (1999) Thymidine phosphorylase gene mutations in MNGIE, a human mitochondrial disorder. Science 283, 689-692 Nishino I, Spinazzola A, Papadimitriou A, Hammans S, Steiner I, Hahn CD, Connolly AM, Verloes A, Guimaraes J, Maillard I, Hamano H, Donati MA, Semrad CE, Russell JA, Andreu AL, Hadjigeorgiou GM, Vu TH, Tadesse S, Nygaard TG, Nonaka I, Hirano I, Bonilla E, Rowland LP, DiMauro S, Hirano M (2000). Mitochondrial neurogastrointestinal encephalomyopathy: an autosomal recessive disorder due to thymidine phosphorylase mutations. Ann. Neurol., 47, 792–800. Nohl H, Gille L, Staniek K. (2005). Intracellular generation of reactive oxygen species by mitochondria. Biochem. Pharmacol. 69, 719-23. Pfanner N. (2000). Protein sorting: recognizing mitochondrial presequences. Curr. Biol. 10, 412-5. Poot M, Zhang YZ, Kramer JA, Wells KS, Jones LJ, Hanzel DK, Lugade AG, Singer VL, Haugland RP. (1996). Analysis of mitochondrial morphology and function with novel fixable fluorescent stains. J Histochem Cytochem. 44, 1363-72. Porcelli AM, Ghelli A, Zanna C, Pinton P, Rizzuto R, Rugolo M. (2005). pH difference across the outer mitochondrial membrane measured with a green fluorescent protein mutant. Biochem. Biophys. Res. Commun. 326, 799-804. Rampazzo C, Ferraro P, Pontarin G, Fabris S, Reichard P, Bianchi V. (2004). Mitochondrial deoxyribonucleotides, pool sizes, synthesis, and regulation. J. Biol. Chem. 279, 17019-26. Saada A, Shaag A, Mandel H, Nevo Y, Eriksson S, Elpeleg O. Mutant mitochondrial thymidine kinase in mitochondrial DNA depletion myopathy. (2001). Nat. Genet., 29, 342-4 Schneider G, Sjoling S, Wallin E, Wrede P, Glaser E, von Heijne G. (1998). Feature-extraction from endopeptidase cleavage sites in mitochondrial targeting peptides. Proteins., 30, 49-60. Singh KK. (1998). Mitochondrial DNA mutations in aging, disease and cancer. Springer, New York, N.Y. Song S, Pursell ZF, Copeland WC, Longley MJ, Kunkel TA, Mathews CK. (2005). DNA precursor asymmetries in mammalian tissue mitochondria and possible contribution to mutagenesis through reduced replication fidelity. Proc. Natl. Acad. Sci. U S A. 102, 4990-5. Song S, Wheeler LJ, Mathews CK. (2003). Deoxyribonucleotide pool imbalance stimulates deletions in HeLa cell mitochondrial DNA. J. Biol. Chem. 278, 43893-6. Su JY, Sclafani RA. (1991). Molecular cloning and expression of the human deoxythymidylate kinase gene in yeast. Nucleic. Acids. Res., 19, 823-7. Tondravi MM, McKercher SR, Anderson K, Erdmann JM, Quiroz M, Maki R, Teitelbaum SL. (1997). Osteopetrosis in mice lacking haematopoietic transcription factor PU.1. Nature. 386, 81-4. Valentine JS, Wertz DL, Lyons TJ, Liou LL, Goto JJ, Gralla EB. (1998). The dark side of dioxygen biochemistry. Curr. Opin. Chem. Biol., 2, 253-62. Voos W, Martin H, Krimmer T and Pfanner N. (1999). Mechanisms of protein translocation into mitochondria. Biochim. Biophys. Acta., 1422, 235–254. Wallace DC. (1999). Mitochondrial diseases in man and mouse. Science. 283, 1482-1488. Wang L, Eriksson S. (2000). Cloning and characterization of full-length mouse thymidine kinase 2: the N-terminal sequence directs import of the precursor protein into mitochondria. Biochem. J. 351, 469-76. Wilusz CJ, Wormington M, Peltz SW. (2001). The cap-to-tail guide to mRNA turnover. Nat. Rev. Mol. Cell. Biol., 2, 237-46. Yakes FM, Van Houten B. (1997). Mitochondrial DNA damage is more extensive and persists longer than nuclear DNA damage in human cells following oxidative stress. Proc. Natl. Acad. Sci. U S A. 94, 514-9. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/36042 | - |
| dc.description.abstract | 為了維持粒腺體DNA的完整性,已知粒腺體中有許多的特殊的激酶 (kinase) 負責合成粒腺體DNA複製與修補所需要的dNTPs,時至今日,已經有數個在粒腺體中扮演這類角色的激酶被發現,包括deoxyribonucleoside kinases (TK2 and dGK) 以及nucleoside diphosphate kinases ( nm23-H4 and nm23-H6) ,然而,尚未有研究指出粒腺體中有dNMP kinase的存在。
本論文的目的即在探索粒腺體中dTMP kinase (TMPK2) 存在的可能性,透過Genebank蛋白質序列的比對以及分析,我們發現TMPK2的可能序列,以RT-PCR的方法將之clone出來,並接上綠色螢光蛋白 (GFP) 基因,形成TMPK2-GFP融合基因後,表現於HeLa細胞中,證明此基因的確為粒腺體的蛋白質,而且其表現可造成細胞內dTTP pool的上升,說明了其在細胞內的功能特性。另外、在大腸桿菌中表現並純化TMPK2,經由活性測試分析也證明了TMPK2具有將dTMP轉換為dTDP的活性。 總括上述,我發現了一個新的粒腺體蛋白質,而且這個蛋白質具有TMPK的活性,為粒腺體內調控dTTP pool的新酵素。 | zh_TW |
| dc.description.abstract | To maintain mitochondrial DNA integrity, mitochondria contain specific kinases for salvage of deoxyribonucleotides. To date, several kinases involved in dNTP synthesis within mitochondria have been identified, including ribonucleoside kinases (TK2 and dGK) and dNDP kinases (nm23-H4 and nm23-H6). However, little is known about mitochondrial dNMP kinases.
In this study, by blast search based on the criteria of conserved TMPK domain and mitochondria targeting sequences, I found a novel mitochondrial protein, designated as TMPK2. The cDNA of TMPK2 encodes a 49 kDa polypeptide, containing a C-terminal conserved TMPK domain and an N-terminus typical mitochondria targeting sequence. By expression of TMPK2-GFP in HeLa cells, I showed that TMPK2 was localized within mitochondria. In parallel, I found that overexpression of TMPK2 increased dTTP pool as TMPK did, suggesting that functional contribution of TMPK2 to intracellular dTTP pool. The enzymatic function of TMPK2 was assessed with recombinant TMPK2 protein. Through NADH-couple TMPK activity assay, I also demonstrated TMPK activity of the recombinant TMPK2 in vitro. In summary, I identified a novel mitochondrial protein with TMPK activity, providing an opportunity to characterize the regulation of dTTP pool within mitochondria. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T07:50:13Z (GMT). No. of bitstreams: 1 ntu-94-R92442014-1.pdf: 2853528 bytes, checksum: 549cdf427320e5f20a44c57f5f90d9b3 (MD5) Previous issue date: 2005 | en |
| dc.description.tableofcontents | 中文摘要……………………..…….1
英文摘要……………………………2 序論…………………………..…….3 實驗方法………………………..…11 實驗結果……………………..……17 討論…………………………..……22 圖表………………………………..26 附錄………………………………..39 參考文獻......................................41 | |
| dc.language.iso | zh-TW | |
| dc.subject | 酸激酶 | zh_TW |
| dc.subject | 胸苷 | zh_TW |
| dc.subject | Thymidylate kinase | en |
| dc.title | 人類粒腺體胸苷酸激酶的分子選殖及分析 | zh_TW |
| dc.title | Molecular cloning and characterization of human mitochondrial thymidylate kinase 2 | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 93-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 陳瑞華,張明富,郭明良 | |
| dc.subject.keyword | 胸苷,酸激酶, | zh_TW |
| dc.subject.keyword | Thymidylate kinase, | en |
| dc.relation.page | 44 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2005-07-26 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 生物化學暨分子生物學研究所 | zh_TW |
| Appears in Collections: | 生物化學暨分子生物學科研究所 | |
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| File | Size | Format | |
|---|---|---|---|
| ntu-94-1.pdf Restricted Access | 2.79 MB | Adobe PDF |
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