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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 羅翊禎(Yi-Chen Lo) | |
| dc.contributor.author | Shin Yen Chong | en |
| dc.contributor.author | 張舜延 | zh_TW |
| dc.date.accessioned | 2021-05-17T10:18:01Z | - |
| dc.date.available | 2015-02-16 | |
| dc.date.available | 2021-05-17T10:18:01Z | - |
| dc.date.copyright | 2012-02-16 | |
| dc.date.issued | 2011 | |
| dc.date.submitted | 2012-01-13 | |
| dc.identifier.citation | 黃丹妮。探討川陳皮素在酵母菌中對紫外線照射引起DNA受損反應的影響；國立台灣大學 食品科技研究所碩士論文：台北市，2010
姜欣怡。綠茶萃出物對維持酵母菌基因穩定性之影響；國立台灣大學 食品科技研究所碩士論文：台北市，2010 Abraham, R.T. (2001). Cell cycle checkpoint signaling through the ATM and ATR kinases. Genes & Development 15, 2177-2196. Arafa, E.S.A., Zhu, Q., Barakat, B.M., Wani, G., Zhao, Q., El-Mahdy, M.A., and Wani, A.A. (2009). Tangeretin Sensitizes Cisplatin-Resistant Human Ovarian Cancer Cells through Downregulation of Phosphoinositide 3-Kinase/Akt Signaling Pathway. Cancer Research 69, 8910-8917. Bachrati, C.Z., and Hickson, I.D. (2003). RecQ helicases: suppressors of tumorigenesis and premature aging. Biochem J 374, 577-606. Bartkova, J., Horejsi, Z., Koed, K., Kramer, A., Tort, F., Zieger, K., Guldberg, P., Sehested, M., Nesland, J.M., Lukas, C., et al. (2005). DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature 434, 864-870. Bassett, D.E., Jr., Boguski, M.S., and Hieter, P. (1996). Yeast genes and human disease. Nature 379, 589-590. 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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/7042 | - |
| dc.description.abstract | 多氧甲基黃酮 (polymethoxyflavones, PMFs) 為柑橘類果皮中含多氧甲基的酚類物質，目前已知其具有廣泛的生理活性，包括抗癌與抗發炎等。先前有許多研究探討PMFs與水解PMFs的抗癌活性，唯目前為止，其在細胞中的作用目標仍不明確。因此，我們利用化合物-基因協調作用的概念，以酵母菌作為研究平台，發掘PMFs在細胞中的可能作用目標。研究顯示，PMFs維持基因穩定上無顯著作用，顯示PMFs不是透過提升細胞的DNA修復因子來達到其生理活性。利用化合物對酵母菌DNA修復基因缺失的突變株作篩選，我們發現sgs1基因突變株在色胺酸被限制的情況下對PMFs成員之一- 橘皮素 (tangeretin) 敏感，無論是在生長速度或是存活率被顯著被抑制。另外，sgs1突變菌株在橘皮素的介入下，其細胞週期會停滯在G1 / S phase，並提升了γH2A的量。透過基因晶片，我們發現橘皮素會抑制sgs1突變株之RNA合成相關的基因的表現量，並提高其含氮化合物與胺基酸的合成基因之表現。透過sgs1突變株對放射菌酮的測試，發現橘皮素並無直接抑制蛋白質合成的效果，反而卻拯救了sgs1與slx4為主的雙股修復相關基因突變株在色氨酸酸剔除或橘皮素介入下的敏感性。結果推測，橘皮素可能是透過抑制sgs1突變株的rRNA的形成，在色胺酸被限制的情況下，間接導致蛋白質合成不利，進而促使菌株死亡。此研究顯示橘皮素在抗癌途徑的可能機制，並發現胺基酸與DNA雙股斷裂修復過程可能存在某種互動關係，唯需進一步實驗驗證。 | zh_TW |
| dc.description.abstract | Polymethoxyflavones (PMFs) is a dietary phytochemical and they have been widely investigated in the field of inflammatory and anti-carcinogenic with proven bioactivities but they actual functioning target in cells remain unclear. Here, we used the model of chemical-genetic interaction model, with budding yeast as platform, to screen the potential targets or pathways involved by PMFs. We found out that SGS1 gene deleted yeast is sensitive to tangeretin, one of a member of PMFs. sgs1 defective yeast showed lower growth rate, survival rate, delayed G1 and S phase and elevated γH2A level in cell cycle under tryptophan drop-out condition. Through microarray, we found out that tangeretin is potential to inhibit expression of RNA progression related genes and up-regulated nitrogen compounds and amino acid synthesis pathways of sgs1 defective cells. Data also showed that tangeretin is incapable to inhibit protein synthesis directly as cycloheximide do. Interestingly, cycloheximide rescued the sensitive- phenotype of sgs1 and slx4 defective cells under tryptophan depletion and tangeretin involved condition. Our results showed tangeretin is potential to suppress rRNA precession of sgs1 defective cells and resulting improper protein synthesis under tryptophan depletion condition. This result demonstrated the potential pathway of anti-carcinogenic effect played by tangeretin. Additionally, we also observed the potential of availability of relationship between amino acid balances and DNA double strains break repair pathways. However, further investigation is required for this observation. | en |
| dc.description.provenance | Made available in DSpace on 2021-05-17T10:18:01Z (GMT). No. of bitstreams: 1 ntu-100-R98641038-1.pdf: 3719824 bytes, checksum: 1a4c02f912856231176e1fe62c2db80a (MD5) Previous issue date: 2011 | en |
| dc.description.tableofcontents | 謝誌 i
摘要 ii Abstract iii 目錄 iv 圖目錄 vi 表目錄 vii 第一章 序論 1 第二章 文獻回顧 3 2.1 多氧甲基黃酮 3 2.1.1 多氧甲基黃酮家族與結構 3 2.1.2多氧甲基黃酮的生理活性 4 2.1.3橘皮素 5 2.2 酵母菌 6 2.2.1 酵母菌為一探討真核生物的實驗模式生物 6 2.2.2 酵母菌為模式生物對人類生命科學的重要性 8 2.2.3 酵母菌為便捷、強大的模式生物 10 2.4 酵母菌SGS1基因 11 2.4.1 酵母菌Sgs1簡介 11 2.4.2 Sgs1與基因的穩定性 13 2.5 DNA複製 15 2.5.1 DNA複製障礙 15 2.5.2 應對複製障礙的機制 17 2.5.3 酵母菌Sgs1與複製叉重啟 20 2.5.4 Sgs1在DNA複製叉與同源重組的功能對細胞的意義 22 2.6 以酵母菌作為探討基因穩定性的平台 25 2.6.1 基因穩定性 25 2.6.2 酵母菌RDKY3615 25 2.7 基因相互作用的關係為一藥物作用目標探索的策略 27 2.7.1 酵母菌基因互動網絡 27 2.7.2 利用基因互動的概念探討藥物的作用目標 28 第三章 研究動機與架構 30 3.1 研究動機 30 3.2 研究架構 30 第四章 材料與方法 32 4.1 實驗藥品與材料 32 4.1.1 酵母菌菌株 32 4.1.2 藥品與培養基 34 4.2 實驗方法 36 4.2.1 酵母菌培養方法 36 4.2.2 酵母菌生長曲線 36 4.2.3 PMFs的介入與酵母菌CAN1基因突變率試驗 36 4.2.4 斑點法 38 4.2.5 酵母菌存活率試驗 38 4.2.6 細胞週期試驗 39 4.2.7 西方墨點法 40 4.2.8 RNA萃取與基因晶片資料分析 43 第五章 結果與討論 45 5.1 橘皮素、川陳皮素與5-去甲基橘皮素不影響野生型菌株的生長 45 5.2 多氧甲基黃酮不能抑制野生型菌株CAN1基因自發性與UV誘導突變 47 5.3 橘皮素能抑制酵母菌sgs1突變株生長 49 5.4 sgs1∆ 酵母菌在YPD與SC-Leu培養基中失去對橘皮素的敏感性 53 5.5 橘皮素促使sgs1∆ 停滯在細胞週期的G1與S期 57 5.6 橘皮素增加sgs1∆ 組蛋白2A的磷酸化 62 5.7 橘皮素影響sgs1∆ RNA合成之功能 66 5.7 橘皮素不具有抑制蛋白質轉譯的功能 74 5.8 綜合討論 76 第六章 結論 79 第七章 參考文獻 80 附錄1 90 附錄2 91 附錄3 94 | |
| dc.language.iso | zh-TW | |
| dc.title | 利用酵母菌之化合物-基因交互作用探討橘皮素作用路徑 | zh_TW |
| dc.title | Investigating Tangeretin Targeted Pathway by Chemical-Genetic Interaction in Yeast | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 100-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 高承福(Cheng-Fu Kao),謝淑貞(Shu-Chen Hsieh),何其儻(Chi-Tang Ho) | |
| dc.subject.keyword | 酵母菌,多氧甲基黃酮,橘皮素,SGS1,化合物-基因協同作用, | zh_TW |
| dc.subject.keyword | yeast,polymethoxyflavones,tangeretin,SGS1,chemical-gene interaction, | en |
| dc.relation.page | 115 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2012-01-13 | |
| dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
| dc.contributor.author-dept | 食品科技研究所 | zh_TW |
| 顯示於系所單位： | 食品科技研究所 | |
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