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研究生:葛孟禹
研究生(外文):Meng-Yu Ke
論文名稱:酵母菌Rsc58蛋白在修復DNA雙股斷裂中角色之探討
論文名稱(外文):Characterization of the Role of Yeast Rsc58p in DNA Double Strand Breaks Repair
指導教授:鄭明媛
指導教授(外文):Ming-Yuan Cheng
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:生命科學暨基因體科學研究所
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:英文
論文頁數:70
中文關鍵詞:RSC複合物RSC58雙股斷裂DNA修復
外文關鍵詞:RSC complexRSC58Double strand breakDNA repair
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酵母菌RSC複合物(染色質結構重組複合物)是屬於ATP依賴性染色質重組複合物(重組者)中SWI/ SNF複合物群。重組者的主要作用是重置(滑動)DNA上的核小體,移除DNA上部分或全部的組蛋白八分體,誘發染色質上DNA對如同轉錄分子或核酸脢等蛋白之接受度的改變,以及將核心型組蛋白置換為多異型的組蛋白[9]。因著重組者在上游的功能,重組者同時控制著其他的染色質行為。近年重組者被證實與DNA雙股斷裂的修復有關[5]。RSC複合物也被證實可能在細胞對DNA損害反應中作為雙股斷裂早期的感應者[8]。而不同的RSC次單元的突變能加強或抑制某些特定之雙股斷裂修復的機制[3, 15]。Rsc58蛋白是一個新發現的RSC複合物次單元,並且Rsc58蛋白的生物功能迄今仍不清楚。在本篇研究中,溫敏性的rsc58突變株被使用於研究Rsc58蛋白在DNA雙股斷裂修復中的生物功能。實驗數據顯示溫敏性rsc58突變株對於紫外光的曝照並沒有或僅有較輕微的敏感性,但有些突變株對能誘發DNA雙股斷裂的抗生素藥物bleomycin或phleomycin具有敏感性。E445K是藥物敏感株中的一株,但yku70Δ/ E445K和yku80Δ/ E445K卻能挽救E445K對bleomycin或phleomycin的敏感性。本實驗也應用了線型化質體的修復試驗。E445K相較於野生型控制組SEY6210對雙股斷裂修復效能較低。然而yku70Δ/ E445K有百分之零點九的比例能在沒有小型同源片段時亦能修復線型化質體,但是yku70Δ/ 6210卻不行。這些數據顯示出Rsc58蛋白可能參與在DNA雙股斷裂的修復中,但關於Rsc58蛋白的詳細機制尚未清楚。而較高解析度和專特的測試將有助於將來Rsc58蛋白在DNA雙股斷裂修復中詳細機制的研究。
Yeast RSC complex (Remodeling the Structure of Chromatin complex) belongs to the family of the SWI/SNF complex of ATP-dependent chromatin remodeling complexes (remodelers). The main functions of remodelers are the reposition (sliding) of nucleosomes on DNA, the removal of part or all of the histone octamer from DNA, an induced change in the accessibility of the DNA in chromatin to proteins such as transcription factors or nucleases, and the exchange of histone variants for core histones [9]. Because of the upstream functions of remodelers, remodelers also control other chromatin behaviors. In recent years, remodelers are demonstrated related to DNA double-stranded breaks (DSB) repair [5]. RSC complex is also demonstrated that RSC complex might be an early DSB sensor in cell’s response to DNA damage [8]. And different mutations of RSC subunits can affect the efficiency of certain DSB repair mechanism [3, 15]. Rsc58p is a newly discovered subunit of RSC complex, and the biological functions of Rsc58p are still unclear. In this study, temperature sensitive rsc58 mutant strains were used to study the biological functions of Rsc58p in DNA DSB repair. The data showed that rsc58ts mutants were non-sensitive or less-sensitive to UV exposure, but some mutants were sensitive to the antibiotic drugs, bleomycin and phleomycin which could induce DNA double-strand break. E445K was one of the drug sensitive strains, but yku70Δ/ E445K and yku80Δ/ E445K could rescue the sensitive phenotype of E445K. According to linearized plasmid repair assay, E445K was less efficient for DSB repair than wild type control, SEY6210. However, yku70Δ/ E445K could repair the linearized plasmid without small homologous fragment with the rate about 0.9 percentages, but yku70Δ/ 6210 could not. These preliminary data showed that Rsc58p might involve in DNA DSB repair pathway, but the detail mechanisms of Rsc58p were not clear. In the future, higher resolution and specificity assays are helpful to study the detail mechanisms of Rsc58p in DNA DSB repair.
誌謝 …………………………………………………… i
摘要 …………………………………………………… ii
Abstract ……………………………………………… iii
Table of Content …………………………………… v
Introduction ………………………………………… 1
Results ………………………………………………… 6
Discussion …………………………………………… 17
Material and Methods ……………………………… 21
Reference ……………………………………………… 27
Figures ………………………………………………… 29
Tables ………………………………………………… 54
Appendix ……………………………………………… 58
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