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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 羅翊禎 | |
| dc.contributor.author | Xiao Tong Teong | en |
| dc.contributor.author | 張曉彤 | zh_TW |
| dc.date.accessioned | 2021-06-08T01:00:22Z | - |
| dc.date.copyright | 2015-02-04 | |
| dc.date.issued | 2014 | |
| dc.date.submitted | 2014-12-31 | |
| dc.identifier.citation | 劉秀琴 2012 能量限制對DNA修復缺陷細胞基因穩定性之影響 國立台灣大學食品科技研究所碩士論文。台北。
羅云君 2013 能量限制增加錯誤配對修復缺陷細胞於老化期間基因的穩定性 國立台灣大學食品科技研究所碩士論文。台北。 (1) Alseth, I.; Eide, L.; Pirovano, M.; Rognes, T.; Seeberg, E.; Bjoras, M. The saccharomyces cerevisiae homologues of endonuclease iii from escherichia coli, ntg1 and ntg2, are both required for efficient repair of spontaneous and induced oxidative DNA damage in yeast. Mol Cell Biol 1999, 19, 3779-3787. (2) Bitterman, K. J.; Medvedik, O.; Sinclair, D. A. Longevity regulation in saccharomyces cerevisiae: Linking metabolism, genome stability, and heterochromatin. Microbiology and molecular biology reviews : MMBR 2003, 67, 376-399, table of contents. (3) Boiteux, S.; Jinks-Robertson, S. DNA repair mechanisms and the bypass of DNA damage in saccharomyces cerevisiae. Genetics 2013, 193, 1025-1064. (4) Boland, C. R.; Goel, A. Microsatellite instability in colorectal cancer. Gastroenterology 2010, 138, 2073-2087 e2073. (5) Brown, K. D.; Rathi, A.; Kamath, R.; Beardsley, D. I.; Zhan, Q.; Mannino, J. L.; Baskaran, R. 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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/18337 | - |
| dc.description.abstract | 熱量限制（Calorie restriction）被認為可延長不同物種間的平均壽命、延緩老化、減少癌症等疾病的發生。若人類的DNA修復系統有缺陷，會增加罹患疾病的可能性，例如：遺傳性非息肉型大腸直腸癌（HNPCC）即是因為錯誤配對修復系統（Mismatch repair, MMR）產生缺陷而致。本研究先前以酵母菌為模式探討熱量限制對老化期間的MMR缺陷細胞的基因穩定性之影響。結果發現熱量限制能延長MMR缺陷細胞壽命和降低突變率。由於細胞中修復點突變的DNA修復有鹼基切除修復系統（Base excision repair, BER）和MMR，且文獻指出熱量限制能正調控BER來促進基因穩定性，因此推測熱量限制可能透過調控BER來降低MMR缺陷細胞的突變率。結果發現熱量限制能有效對老化期間MMR/BER缺陷細胞延緩壽命、增強細胞抵禦受損能力和維持基因穩定性，老化期間MMR缺陷細胞中BER基因表現量也不受熱量限制影響。因而透過RNA-seq分析熱量限制可能對MMR缺陷細胞的基因群影響，發現MMR缺陷細胞經熱量限制後的乙醛酸代謝和脂肪酸代謝相關的生理功能顯著被調控。隨後研究發現若老化期間無熱量限制介入時，利用hydroxyurea減緩細胞週期可使MMR缺陷細胞維持基因穩定性但無法延緩壽命，顯示細胞週期的調控的確可以影響基因的穩定性。另一方面，研究也發現在熱量限制的細胞中，參與DNA雙股螺旋斷裂修復路徑（Double strand break repair, DSBR）的H2A蛋白磷酸化增加。綜合本篇研究結果，推測熱量限制可維持老化期間MMR缺陷細胞中基因的穩定性和延緩壽命的現象，是否經由調控細胞週期的變化和DSBR的修復能力仍需進一步的深入研究。 | zh_TW |
| dc.description.abstract | Calorie restriction (CR) is able to reduce cancer progression and extend life span in various organisms. Age-related decline of DNA repair system such as mismatch repair (MMR) can reverse by CR. Defects in MMR have been linked to colorectal and sporadic cancers. Our previous results have demonstrated that CR can extend life span and maintain genome stability in MMR-defected cells during aging, but the mechanisms are poorly understood. Therefore, we suggest base excision repair (BER) which has been proven can be up-regulated by CR, is responsible to maintain genome stability in MMR-defected cells. However, we found that CR still able to extend life span and reduce mutations in MMR/BER -defected cells. And, CR has no effect on BER gene expression in MMR-defected cells during aging. To investigate the mechanisms responsible for CR to maintain genome stability in MMR-defected cells, the whole genome profile by performing RNA-seq has been analyzed. The most significant influenced genes which regulated by CR in MMR-defected cells are fatty acid metabolism, glyoxylate and dicarboxylate metabolism pathways. Besides, we demonstrate by using hydroxyurea to slow down cell cycle progression can maintain genome stability without CR in MMR-defected cells during aging, 50mM HU can reduce mutation by patching assay, however, HU also reduce life span in cells. Furthermore, we found that phosphorylation levels of H2A in CR cells are higher than non-CR cells. H2A phosphorylation is a marker of double strand break repair (DSBR). Further studies are needed to investigate whether CR would beneficial to MMR-defected cells through affecting cell cycle and DSBR pathway. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-08T01:00:22Z (GMT). No. of bitstreams: 1 ntu-103-R01641042-1.pdf: 4463012 bytes, checksum: 7fed0b78a8e1535f91b7560b21ed81b5 (MD5) Previous issue date: 2014 | en |
| dc.description.tableofcontents | 口試委員審定書 1
謝誌 II 摘要 III Abstract IV 目錄 V 圖目錄 VIII 表目錄 IX 縮寫對照表 X 第一章 前言 1 第二章 文獻整理 2 第一節 老化與基因不穩定性 2 一、 老化現象 2 二、 基因不穩定 4 三、 酵母菌的老化模式 4 第二節 熱量限制 6 第三節 DNA修復系統 9 一、 錯誤配對修復 (Mismatch repair, MMR) 9 二、 鹼基切除修復 (Base excision repair, BER) 13 三、 雙股螺旋斷裂修復（Double strand break repair, DSBR） 15 第三章 實驗設計 16 第四章 材料與方法 18 第一節 材料 18 一、 酵母菌株 18 二、 培養基種類 19 第二節 實驗方法 22 一、 酵母菌培養方式 22 二、 酵母菌存活數 (Cell viability test) 22 三、 點試驗 (Spotting assay) 22 四、 突變率定性 (Patching assay) 和定量試驗 22 五、 RNA萃取與RNA-seq全基因體資料分析 23 六、 即時聚合酶鏈式反應 (qPCR) 24 七、 HU treatment assay 25 八、 西方墨點法 (Western Blot) 25 九、 統計分析 26 第五章 結果與討論 28 第一節 熱量限制可延長MMR和BER缺陷細胞的壽命 28 第二節 不同DNA受損形式下BER缺陷對細胞於老化及熱量限制期間之影響 31 第三節 熱量限制增加MMR和BER缺陷細胞於老化期間基因穩定性 36 第四節 熱量限制對wild type和msh2∆msh3∆細胞的BER基因表現影響 42 第五節 熱量限制的介入對wild type 和msh2∆msh3∆細胞全基因體變化之影響 44 第六節 細胞週期的減緩會降低msh2∆msh3∆細胞的基因突變率 64 第七節 熱量限制對老化期間wild type和msh2∆msh3∆ 細胞的H2A蛋白磷酸化表現量 68 第六章 討論 70 第七章 結論 73 第八章 參考文獻 74 第九章 附錄 79 附錄1 79 附錄2 81 附錄3 84 | |
| dc.language.iso | zh-TW | |
| dc.title | 熱量限制對錯誤配對修復缺陷細胞於老化期間全基因體之變化 | zh_TW |
| dc.title | Study of calorie restriction using RNA-sequencing profiling in mismatch repair defected cells during chronological aging in Saccharomyces cerevisiae | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 103-1 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 謝淑貞,高承福 | |
| dc.subject.keyword | 熱量限制,錯誤配對修復缺陷,細胞週期,老化,基因穩定, | zh_TW |
| dc.subject.keyword | calorie restriction,mismatch repair,cell cycle,aging,genome stability, | en |
| dc.relation.page | 85 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2014-12-31 | |
| 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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