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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 張智芬 | |
| dc.contributor.author | Yi-Chang Chang | en |
| dc.contributor.author | 張益昌 | zh_TW |
| dc.date.accessioned | 2021-06-13T04:46:35Z | - |
| dc.date.available | 2006-08-04 | |
| dc.date.copyright | 2006-08-04 | |
| dc.date.issued | 2006 | |
| dc.date.submitted | 2006-07-17 | |
| dc.identifier.citation | References
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/33546 | - |
| dc.description.abstract | 細胞產生胸苷三磷酸 (dTTP) 的過程被嚴密的調控著，在細胞週期進行時此過程也協同DNA 的複製。 我們過去的研究指出，在 DNA複製完成後，細胞分裂後期促進複合體 (anaphase promoting complex/cyclosome, APC/C) 對人類胸腺嘧啶激酶 (human thymidine kinase 1, hTK1) 及人類胸苷酸激酶 (human thymidylate kinase, hTMPK) 的蛋白降解途徑在調控 dTTP pool 上扮演重要的角色。 在本研究中，我證明了在生長停滯的細胞中，胸腺嘧啶 (thymidine) 與人類胸腺嘧啶激酶 (hTK1) 的結合可防止人類胸腺嘧啶激酶 (hTK1) 被 APC/C-Cdh1 所從屬的降解機制所降解。 穩定表現原生型人類胸腺嘧啶激酶 (wild type hTK1) 及原生型人類胸苷酸激酶 (wild type hTMPK) 的 NIH3T3 纖維組織母細胞 (fibroblasts) 在細胞生長方面對於胸腺嘧啶 (thymidine) 的處理相當敏感。 藉由流式細胞分析技術，我發現在血清刺激 (serum stimulation) 的條件下，有胸腺嘧啶 (thymidine) 處理過的細胞具有 S phase 進行緩慢的現象。 雖然在剝奪血清 (serum deprivation) 時人類胸腺嘧啶激酶 (hTK1) 可以被胸腺嘧啶 (thymidine) 所穩定，但這樣的情況並不會導致 dTTP pool 在同時表現人類胸腺嘧啶激酶 (hTK1) 及人類胸苷酸激酶 (hTMPK) 的細胞中顯著上升。 事實上，在剝奪血清 (serum deprivaiton) 的過程中即使人類胸腺嘧啶激酶 (hTK1) 沒有被穩定，在血清刺激 ( serum stimulation) 下處理胸腺嘧啶 (thymidine) 這些細胞仍顯示 G1/S phase 停溜的現象，而在此停溜的過程中我都沒有觀察到 dNTP 不平衡及去氧胞苷三磷酸 (dCTP) 缺乏的現象。 在此期間，胸腺嘧啶所誘發的 G1/S phase 停溜伴隨著檢查點 (checkpoint) 的活化，而此過程中不需要 Chk2 的活性。 另一方面，提供去氧胞苷 (deoxycytidine) 可以挽回胸腺嘧啶 (thymidine) 誘發的 G1/S phase 停溜現象，這樣的結果指出複製過程的檢查點 (checkpoint) 並非直接因為缺乏去氧胞苷三磷酸 (dCTP) 而活化，而是藉由一個機制去檢測 dNTP 的不平衡最後導致檢查點 (checkpoint) 的活化。 | zh_TW |
| dc.description.abstract | Cellular production of dTTP is a highly regulated process that is coordinated with DNA replication in the cell cycle. Our previous study has shown that the down-regulation of human TK1 (hTK1) and human TMPK (hTMPK) proteins by APC/C (anaphase promoting complex/cyclosome)-mediated proteolysis pathway plays an important role in the regulation of dTTP pool after completion of DNA replication in the cell cycle. In this study, I showed that thymidine binding prevents hTK1 from APC/C-Cdh1-mediated degradation, rendering its stabilization during growth arrest. Cell proliferation of NIH3T3 fibroblasts stably expressing hTK1 and hTMPK were sensitive to thymidine treatment. By FACS analysis, I found that these cells treated with thymidine had slow S phase progression in response to serum stimulation. Although hTK1 is stabilized during serum deprivation by thymidine, this condition did not induce a drastic increase of dTTP level in wt/wt cells. In fact, without hTK1 stabilization during serum deprivation, these cells still displayed the G1/S phase arrest after serum stimulation in the presence of thymidine, where neither a severe dNTP imbalance nor was the dCTP depletion detected. In the meanwhile, thymidine-induced G1/S phase arrest was accompanied by increased extent of checkpoint activation without the requirement for Chk2 activity. Since the supply of deoxycytidine could still rescue the thymidine-induced G1/S arrest, the results indicated that the onset of replication checkpoint activation may occur due to a mechanism sensing dNTP imbalance rather than a direct consequence of dCTP depletion during DNA replication. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T04:46:35Z (GMT). No. of bitstreams: 1 ntu-95-R93442015-1.pdf: 1402925 bytes, checksum: 66574c1d384708563fc1fc66c0bd24c0 (MD5) Previous issue date: 2006 | en |
| dc.description.tableofcontents | 目錄
中文摘要…………………………………………………………. 1 Abstract………………………………………………………….. 2 Introduction……………………………………………………... 3 Materials and Methods…………………………………………. 10 Results…………………………………………………………… 16 Discussion……………………………………………………….. 23 Figures and Legends……………………………………………. 26 Appendix………………………………………………………... 44 References………………………………………………………. 45 | |
| dc.language.iso | en | |
| dc.subject | 細胞週期 | zh_TW |
| dc.subject | 胸腺嘧啶 | zh_TW |
| dc.subject | 胸腺嘧啶激酶 | zh_TW |
| dc.subject | TK | en |
| dc.subject | thymidine | en |
| dc.subject | cell cycle | en |
| dc.title | 胸腺嘧啶對人類胸腺嘧啶激酶穩定性及細胞週期影響之探討 | zh_TW |
| dc.title | Effects of thymidine on hTK1 stabilization and cell cycle progression | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 94-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 張明富,陳美如,李芳仁 | |
| dc.subject.keyword | 胸腺嘧啶激酶,細胞週期,胸腺嘧啶, | zh_TW |
| dc.subject.keyword | TK,thymidine,cell cycle, | en |
| dc.relation.page | 52 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2006-07-18 | |
| 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 |
| 顯示於系所單位： | 生物化學暨分子生物學科研究所 | |
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