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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 羅?升(Wan-Sheng Lo) | |
| dc.contributor.author | Wei-Han Lin | en |
| dc.contributor.author | 林暐瀚 | zh_TW |
| dc.date.accessioned | 2021-06-15T11:11:46Z | - |
| dc.date.available | 2019-08-26 | |
| dc.date.copyright | 2016-08-26 | |
| dc.date.issued | 2016 | |
| dc.date.submitted | 2016-08-22 | |
| dc.identifier.citation | Allen, C., S. Buttner, A. D. Aragon, J. A. Thomas, O. Meirelles, J. E. Jaetao, D. Benn, S. W. Ruby, M. Veenhuis, F. Madeo and M. Werner-Washburne (2006). 'Isolation of quiescent and nonquiescent cells from yeast stationary-phase cultures.' J Cell Biol 174(1): 89-100.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/48930 | - |
| dc.description.abstract | 對生物體來說，老化是一個必然會發生的生理過程，而老化被認為是造成疾病與死亡的風險因子之一。老化發生的機制仍有許多未解之謎，而在過往的十年中，其相關的研究已經發展至分子生物的層次，因此，以單一細胞做為一個獨立個體的出芽酵母提供了一個極好的模型來研究高等真核生物的老化機制。在本篇論文中，我利用酵母菌的世代壽命 (chronological lifespan, CLS) 模型來進行老化的研究。由於染色體的動態變化被認為是老化過程中重要的調控方式之一，因此本篇論文之研究方向主要是想探討酵母菌的H3K36去甲基酶Rph1在老化過程中扮演的角色。
在第一部分中，我使用內源性表達Rph1之細胞作為研究材料。首先，本研究發現Rph1對於老化的酵母菌之熱耐受性是十分重要的，而且其功能性區域zing-finger與JmjN對於熱耐受性皆是不可或缺的，但失去Rph1去甲基酶活性的細胞則不會對於其熱耐受性有明顯的影響。此外，Rph1可能會參與細胞週期的調控，並對於細胞進入與離開靜止期(stationary phase)有其重要的功能。再者，本研究亦發現酵母菌會藉由調控Rph1磷酸化與去磷酸化等轉譯後修飾的方式來控制其在不同時期之功能，而此調控機制可能是受到Rim15相關的訊號傳遞路徑來調控的。除了轉譯後修飾之外，本研究也發現在老化過程中，細胞會藉由調控Rph1信使RNA的轉錄與Rph1蛋白質的量來控制Rph1的功能。而在第二部分中，本研究發現過度表達Rph1會造成細胞延長其生長遲滯期(lag phase)，而異位表達Rph1則會提高細胞在老化時期的熱耐受性。綜合上述結果，本研究指出H3K36去甲基酶Rph1參與在酵母菌細胞進入老化的進程以及老化細胞回到適當環境後重新啟動生長等重要的過程。 | zh_TW |
| dc.description.abstract | Aging is an inevitable biological process leading to death and remains as a long-standing mystery in biology. In the last decade, research of aging has been advanced extensively into the molecular level. The single-celled Saccharomyces cerevisiae (budding yeast) is an excellent model organism to study the molecular and cellular events of chronological lifespan (CLS) in eukaryotes. Chromatin dynamics has been appreciated as one of the master modulators in aging process. Therefore, my thesis research focuses on the mechanistic roles of H3K36 demethylase Rph1 in regulation of the CLS in S. cerevisiae.
First, I investigated the functional roles of Rph1 expressed by its own promoter in response to stress condition during chronological aging. I showed that Rph1 is required for thermotolerance in aging yeast. The functional domains of Rph1, zing finger (ZF) and JmjN, but not the catalytic domain for demethylase activity, contribute to the thermotolerance activity in aging cells. In addition, Rph1 is likely involved in cell cycle progression, quiescence entry and exit. Furthermore, Rph1 is hyper-phosphorylation upon diauxic-shift and hypo-phosphorylation upon re-feeding and such reversible protein phosphorylation of Rph1 is Rim15-dependent during CLS. In the second part of my work, I found that constitutively expressed and overexpressed Rph1 prolong the lag phase of earlier cell growth. Furthermore, the higher expressed Rph1 enhanced the thermotolerance of aging yeast in stationary phase, suggesting that the expression of Rph1 is highly regulated and consequently to control cell growth in chronological aging. Taken together, my work reveals the functional roles of Rph1 in regulation of yeast CLS and further demonstrates the post-translational modifications contribute to modulate Rph1 on aging and/or rejuvenation process. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T11:11:46Z (GMT). No. of bitstreams: 1 ntu-105-R03442023-1.pdf: 56921923 bytes, checksum: 91d51c4ee1b08093ae3b64b4e6db0f95 (MD5) Previous issue date: 2016 | en |
| dc.description.tableofcontents | 口試委員會審定書 #
誌謝 i 中文摘要 ii ABSTRACT iii CONTENTS v LIST OF FIGURES ix LIST OF TABLES xi Chapter 1 Introduction 1 1.1 Aging is a risk factor for disease 1 1.2 Two major models for aging study in Saccharomyces cerevisiae 1 1.3 The chronological life span (CLS) in yeast 3 1.4 Two major molecular pathways modulating CLS in yeast 4 1.5 Rph1 and Gis1 are two paralogous JmjC-domain containing proteins 5 1.6 Rph1 regulates the transcription of environment stress response (ESR) genes 7 1.7 Rph1 is probable to regulate chronological aging 8 Chapter 2 Materials and Methods 12 2.1 Yeast strains and growth media 12 2.2 Plasmid construction and preparation 12 2.3 Thermotolerance assay 13 2.4 Reverse transcription 13 2.5 Real-time quantitative PCR (qPCR) 13 2.6 Protein extracts preparation by Trichloro acetic acid (TCA) precipitation 14 2.7 Western blot 14 2.8 Colony formation unit (CFU) analysis 15 2.9 Survival rate and PI staining 15 2.10 Flow cytometry 16 2.11 NQ and Q cells separation 16 Chapter 3 Results 18 3.1 Functional and mechanistic studies of H3K36 demethylase Rph1 during chronological aging in Saccharomyces cerevisiae 18 3.1.1 Rph1 is required for thermotolerance in aging yeast 18 3.1.2 The JmjN and zing-finger domains, but not the histone demethylase activity of Rph1, are necessary for the thermotolerance during aging 19 3.1.3 The rph1 mutants display different cell viability maintenance during CLS 20 3.1.4 Rph1 is involved in the cell cycle regulation 22 3.1.5 The rph1∆ delays the quiescence entry in CLS 23 3.1.6 The stationary phase yeast culture can be separated into two distinct cell populations 24 3.1.7 Loss of Rph1 delays cell cycle re-entry at quiescent stage 26 3.1.8 Rph1 plays different roles in transcriptional regulation of ESR and autophagy genes during CLS 26 3.1.9 After diauxic-shift, the RPH1 transcription level was induced but the protein level of Rph1 reduced dramatically 27 3.1.10 Rph1 is regulated by phosphorylation and dephosphorylation during CLS and after re-feeding 28 3.1.11 The phosphorylation of Rph1 is regulated by Rim15 during CLS 29 3.1.12 The phosphorylation of Rph1 is important during CLS 30 3.2 The effects of different expression levels of H3K36 demethylase Rph1 during chronological aging in Saccharomyces cerevisiae 32 3.2.1 Constitutively expressed and over-expressed Rph1 prolong the lag phase 32 3.2.2 Constitutively expressed Rph1 enhanced the thermotolerance during aging 33 3.2.3 The transcription level and protein level were controlled during CLS 33 Chapter 4 Discussion 35 4.1.1 The transcription regulation of acetate, acetyl-CoA and glycerol metabolisms by Rph1 during post-diauxic shift may contribute to the cell viability maintenance 35 4.1.2 The histone demethylase activity of Rph1 and the longevity 37 4.1.3 Rph1 is involved in the cell cycle regulation, quiescence entry and cell cycle re-entry 38 4.1.4 The Rph1 protein level reduced during CLS 39 Chapter 5 Figures and legends 41 Chapter 6 Tables 58 References 60 | |
| dc.language.iso | en | |
| dc.subject | Rph1 | zh_TW |
| dc.subject | 組蛋白去甲基? | zh_TW |
| dc.subject | 世代壽命 | zh_TW |
| dc.subject | 老化 | zh_TW |
| dc.subject | Rph1 | en |
| dc.subject | H3K36 demethylase | en |
| dc.subject | chronological life span | en |
| dc.subject | aging | en |
| dc.title | 探討酵母菌去甲基酶Rph1在世代壽命中之功能與調控機制 | zh_TW |
| dc.title | Functional and mechanistic studies of the H3K36 demethylase Rph1 during the chronological life span in Saccharomyces cerevisiae | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 104-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 林敬哲,鄧述諄,王隆祺 | |
| dc.subject.keyword | 世代壽命,組蛋白去甲基?,Rph1,老化, | zh_TW |
| dc.subject.keyword | chronological life span,H3K36 demethylase,Rph1,aging, | en |
| dc.relation.page | 66 | |
| dc.identifier.doi | 10.6342/NTU201603541 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2016-08-22 | |
| 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 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-105-1.pdf 未授權公開取用 | 55.59 MB | Adobe PDF |
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