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http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/61217完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 羅翊禎 | |
| dc.contributor.author | Pei-Shang Wu | en |
| dc.contributor.author | 巫佩珊 | zh_TW |
| dc.date.accessioned | 2021-06-16T10:53:48Z | - |
| dc.date.available | 2018-08-28 | |
| dc.date.copyright | 2013-08-28 | |
| dc.date.issued | 2013 | |
| dc.date.submitted | 2013-08-09 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/61217 | - |
| dc.description.abstract | 細胞的DNA複製需經由嚴密的監控以確保細胞遺傳訊息傳遞的完整性和忠實性。一般認為，在DNA複製的過程中會影響複製叉移動或複製叉結構的因素都可能造成DNA複製壓力，進而導致複製叉暫停。在酵母菌 (Saccharomyces cerevisiae) 的模式中，複製叉的暫停會活化複製監控點 ─ Mec1/Rad53路徑以減緩細胞複製週期的進行並且穩定複製叉的結構。鑒於酵母菌解旋酶 Sgs1與錯配修復辨認蛋白個別與Mec1/Rad53路徑的訊息傳遞有關，本實驗藉由hydroxyurea (HU) 和methylmethane sulfonate (MMS) 的處理來探討Sgs1與錯配修復辨認蛋白在複製壓力下的交互作用。在一般生長狀態下，SGS1與MSH2的同時缺失導致細胞週期的調控異常；相對於野生型其突變率顯著增加。雖然其它基因的缺失 (msh3Δmsh6Δ, sgs1Δmsh3Δ及sgs1Δmsh6Δ突變菌株) 會造成酵母菌的世代時間增長，僅有SGS1與MSH2的同時缺失會導致細胞在慢性HU或MMS的處理下細胞存活率比單一基因的缺失要來得低。從complementation tests的結果推論細胞在面臨DNA複製壓力下除了需要Sgs1的解旋活性及Sgs1與DNA拓樸異構酶Top3的鍵結之外，同時需要Msh2的參與。此外，在急性HU的處理下，sgs1Δmsh2Δ 的Rad53活化並未受到影響。然而，在HU被移除後，sgs1Δmsh2Δ從DNA複製壓力中回復的能力減弱，並有較多的細胞停滯在G2/M phase。從Hoechst染色的結果，有絲分裂期染色體的分離異常可能不是導致sgs1Δmsh2Δ突變菌株在複製壓力被移除後細胞死亡的主要原因。因此，在DNA複製壓力下，除了已知的Sgs1之外，Msh2可能與穩定複製叉的結構有關。在SGS1與MSH2同時缺失的情況下，暫停的複製叉可能因而斷裂而促使細胞在進入有絲分裂前死亡。 | zh_TW |
| dc.description.abstract | Replicative stress in general refers to conditions that influence the progression and/or structure integrity of replication forks. Stalled forks would generate single strand DNA regions that bounded by RPA, which in turn triggers activation of replication checkpoint - the Mec1-Rad53 pathway in Saccharomyces cerevisiae. Functional interaction between RecQ helicase Sgs1 and mismatch repair recognition proteins in response to replicative stress is of interest due to the fact that they are showed to separately involve in the Mec1 signaling pathway. Loss of SGS1 and MSH2 are found to cause defect in cell cycle under normal growth condition and additive increases in accumulating mutation rates. The interaction between Sgs1 and MMR protein under replicative stress was tested by treatments of hydroxyurea (HU) and methylmethane sulfonate (MMS) that interfere with DNA replication. Although slow growth phenotypes are observed in msh3Δmsh6Δ, sgs1Δmsh3Δ, and sgs1Δmsh6Δ mutants, only the sgs1Δmsh2Δ show synergistic cell death under chronic HU and MMS treatments. From complementation tests, helicase activity and Top3 binding are found to be required for Sgs1 under replicative stress that specifically dependent on Msh2 but not Msh3 and Msh6. Activation of Rad53 is not compromised in asynchronized sgs1Δmsh2Δ mutants during the period of HU treatment. However, deletions of both SGS1 and MSH2 genes cause moderate decrease in ability to recover from prolonged HU treatment in parallel with G2/M arrest. Further, mitotic missegregation event might not be responsible for the low recovery of sgs1Δmsh2Δ mutants after HU treatment. Functional redundancy between Msh2 and Sgs1 in maintenance of stalled replication forks is then proposed. With the absence of both Sgs1 and Msh2, stalled replication forks might have in turn collapse thereby causing cell death before cell entry into mitosis. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T10:53:48Z (GMT). No. of bitstreams: 1 ntu-102-R00641011-1.pdf: 4433320 bytes, checksum: 6d0cf0e6b2c3b49bb0acf9ba27cb62f3 (MD5) Previous issue date: 2013 | en |
| dc.description.tableofcontents | TABLE OF CONTENTS
謝誌 i ABSTRACT ii 中文摘要 iii TABLE OF CONTENTS iv LIST OF FIGURES vii LIST OF TABLES viii CHAPTER 1. INTRODUCTION 1 1.1 Cellular responses to replicative stress 1 1.2 The family of RecQ helicases 2 1.2.1 Sgs1 in recombination and replication 3 1.2.2 Separate roles of Sgs1 in checkpoint 4 activation and maintenance of replication forks 1.3 Mismatch repair 5 1.3.1 Mismatch repair in S phase 6 1.3.2 Mismatch repair proteins in DNA damage 6 signaling 1.4 The aims of study 8 CHAPTER 2. MATERIALS AND METHODS 9 2.1 Strains, plasmids, and media 9 2.2 Plasmids isolation 9 2.3 Yeast constructions 10 2.4 Growth curves 12 2.5 Cell cycle analysis 12 2.6 Mutation rates 13 2.7 Chronic treatments 14 2.8 Acute HU treatments 15 2.9 Budding index analyses 16 2.10 Hoechst staining 18 2.11 Statistical analyses 18 CHAPTER 3. RESULTS 21 3.1 Loss of SGS1 and MSH2 could cause defect in cell 21 cycle regulation 3.2 Mutation rates revealed different dependency of 22 Msh2 and Sgs1 on maintenance of genome stability 3.3 Sgs1 and Msh2 could have interaction under 22 persistent replicative stress 3.4 Helicase activity and Top3 binding of Sgs1 are 23 required for cell survival under replicative stress in the absence of Msh2 3.5 Activation of Rad53 is not abolished in 26 asynchronized sgs1Δmsh2Δ mutants 3.6 Recovery defect and G2/M arrest after HU 27 treatment in sgs1Δmsh2Δ mutants 3.7 Mitotic missegregation event in sgs1Δmsh2Δ after 28 HU treatment CHAPTER 4. DISCUSSION 29 4.1 Defect of sgs1Δmsh2Δ mutants in S/M phase 29 transition 4.2 Sgs1 specifically interacts with Msh2 in 30 response to replicative stress 4.3 Hypermorphic phenotype of sgs1-V29E allele 31 4.4 Possible redundant role of Sgs1 and Msh2 under 32 replicative stress 4.5 Conclusion 33 REFERENCES 34 MANUSCRIPT (draft) 57 | |
| dc.language.iso | en | |
| dc.subject | Mec1/Rad53路徑 | zh_TW |
| dc.subject | 複製叉暫停 | zh_TW |
| dc.subject | Sgs1 | zh_TW |
| dc.subject | Msh2 | zh_TW |
| dc.subject | Msh2 | en |
| dc.subject | stalled replication forks | en |
| dc.subject | Sgs1 | en |
| dc.subject | Mec1/Rad53 pathway | en |
| dc.title | 酵母菌Msh2與解旋酶Sgs1於DNA複製壓力下的功能重複 | zh_TW |
| dc.title | Functional redundancy between Msh2 and Sgs1 helicase under replicative stress in Saccharomyces cerevisiae | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 101-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 董桂書,高承福,謝淑貞 | |
| dc.subject.keyword | 複製叉暫停,Sgs1,Msh2,Mec1/Rad53路徑, | zh_TW |
| dc.subject.keyword | stalled replication forks,Sgs1,Msh2,Mec1/Rad53 pathway, | en |
| dc.relation.page | 80 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2013-08-09 | |
| 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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