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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 李財坤(Tsai-Kun Li) | |
| dc.contributor.author | Han-Wen Chang | en |
| dc.contributor.author | 張涵雯 | zh_TW |
| dc.date.accessioned | 2021-06-13T06:37:59Z | - |
| dc.date.available | 2007-08-03 | |
| dc.date.copyright | 2006-08-03 | |
| dc.date.issued | 2006 | |
| dc.date.submitted | 2005-07-26 | |
| dc.identifier.citation | Abraham, R.T. (2001) Cell cycle checkpoint signaling through the ATM and ATR kinases. Genes Dev, 15, 2177-2196.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/34976 | - |
| dc.description.abstract | 最近的研究發現，哺乳動物具有兩個 DNA 拓樸酶III之同功酶 － TOP3α 和 TOP3β ，致使科學家們感興趣於剖析兩個同功酶各自的酵素活性及功能。在本篇研究中，我們利用酵母菌雙雜交以及 RNA 干擾壓制細胞內基因表現的技術，找出和 hTOP3 同功酶有交互作用的蛋白質候選者且推論 hTOP3 同功酶在細胞內可能的功能；且分別勾勒兩個 hTOP3 同功酶的蛋白質交互作用圖譜亦應可使我們區分兩者分別的細胞功能。依據實驗結果，我們發現與 hTOP3α 同功酶有交互作用的蛋白質候選者在數量上和種類上都跟與 hTOP3β 同功酶有交互作用的蛋白質候選者不同。我們也檢測了兩個 hTOP3 同功酶的基因表現程度，結果顯示： hTOP3α基因表現在 G1/S 時期達到最高，而 hTOP3β則是在 G2/M 時期為高峰；此外， hTOP3α在腫瘤組織的基因表達程度較同來源的正常組織低。令人驚訝的，我們發現了 hTOP3α在細胞週期檢控點的調控上扮演角色，而這樣的調控很有可能是經由轉錄機制調控細胞週期檢控點相關蛋白的表現量。總括以上，我們的實驗結果支持了兩個 hTOP3 同功酶有不同功能的假設，且 hTOP3α在 S 時期檢控點上扮演重要的角色。除此之外，由於 hTOP3α在腫瘤組織的基因表達較低且 hTOP3α在細胞週期檢控點的調控上扮演角色，因此我們推測 hTOP3α可能作為一腫瘤抑制因子。兩個 hTOP3 同功酶在細胞瘤化上是否扮演不同的角色亦在本篇論文中被討論。 | zh_TW |
| dc.description.abstract | Recent identification of two DNA topoisomerase III isoforms, TOP3α and TOP3β , in mammalian cells has promoted great interests to dissect iozyme-specific activities and functions. In this thesis, we took advantage of the well-developed yeast 2-hybrid system and RNA interference gene-knockdown technology to identify potential TOP3-interacting proteins and to determine the potential cellular functions of hTOP3 isozymes. Mapping out different interacting protein of two human TOP3 isozymes should also enable us to differentiate their cellular functions. Indeed, the spectrum of potential hTOP3-interating proteins differs both qualitatively and quantitatively from that of potential hTOP3-interating proteins. We also examined the gene expression profiles of two hTOP3 isoforms, which pointed to the following conclusion: hTOP3α level reaches prime in G1/S phase, while the highest expression of hTOP3β is observed during G2/M stage. Furthermore, the expression levels of hTOP3α has been shown to be lower in tumor tissues compared to the corresponding normal tissues. Most striking, we observed the role of hTOP3α in regulating the activation of cell cycle checkpoint, possibly through controlling on the transcription levels of checkpoint proteins. Taken together, our results suggest that two hTOP3 isozymes exhibit different cellular functions with hTOP3α plays a major role in S-phase checkpoint regulation. In addition, the lower expression level of hTOP3α in cancerous tissues and potential role of hTOP3α in cell cycle checkpoint regulation have led us speculate that hTOP3α might act as a tumor suppressor. The differential roles of TOP3 isozymes in turmogenesis are also discussed. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T06:37:59Z (GMT). No. of bitstreams: 1 ntu-95-R92445112-1.pdf: 6271736 bytes, checksum: 5915c9e22ef399d23c227022f1deef10 (MD5) Previous issue date: 2006 | en |
| dc.description.tableofcontents | 目錄……………………………………………………………………I
英文摘要………………………………………………………………II 中文摘要………………………………………………………………III 緒論……………………………………………………………………1 研究目標………………………………………………………………15 材料與方法……………………………………………………………16 結果……………………………………………………………………26 討論……………………………………………………………………33 參考文獻………………………………………………………………40 圖表……………………………………………………………………46 | |
| dc.language.iso | zh-TW | |
| dc.title | 人類DNA拓樸異構酶Ⅲ的功能研究 | zh_TW |
| dc.title | Functional Study on Human DNA Topoisomerase Ⅲ | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 94-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 董馨蓮(Shin-Lian Doong),鄧述諄(Shu-Chun Teng) | |
| dc.subject.keyword | 拓樸異構酶,細胞週期,蛋白質複合體,拓樸酶,III, | zh_TW |
| dc.subject.keyword | topoisomerase III,cell cycle checkpoint,protein complex,top3, | en |
| dc.relation.page | 63 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2005-07-27 | |
| 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 | |
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