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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 方偉宏(Woei-horng Fang) | |
| dc.contributor.author | Yi-Ying Liu | en |
| dc.contributor.author | 劉懿瑩 | zh_TW |
| dc.date.accessioned | 2021-06-13T05:50:25Z | - |
| dc.date.available | 2009-08-02 | |
| dc.date.copyright | 2006-08-02 | |
| dc.date.issued | 2006 | |
| dc.date.submitted | 2006-07-06 | |
| dc.identifier.citation | Au KG, Welsh K, Modrich P. (1992) Initiation of methyl-directed mismatch repair.
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Pharmaco.l 36, 326–335 Sunderman FW Jr., Oskarsson A. (1991) Metals and Their Compounds in the Environment. Analysis and Biological Relevance. 1101–1126 Sura P, Ristic N, Bronowicka P, Wrobel M. (2006) Cadmium toxicity related to cysteine metabolism and glutathione levels in frog Rana ridibunda tissues. Comp. Biochem. Physiol. C. Toxicol. Pharmacol. 142, 128-135. Su SS, Lahue RS, Au KG, Modrich P. (1988) Mispair specificity of methyl-directed DNA mismatch correction in vitro. J. Biol. Chem. 263, 6829-6835 Thomas DC, Roberts JD, Kunkel TA. (1991) Heteroduplex repair in extracts of human HeLa cells. J. Biol. Chem. 266, 3744-3751 Tjalve H, Jasim S, Oskarsson A. (1984) Nickel mobilization by sodium diethyldithiocarbamate in nickel-carbonyl treated mice. Nickel in the Human Environment. 311–320 Umar A, Buermeyer AB, Simon JA, Thomas DC, Clark AB. (1996) Requirement for PCNA in DNA mismatch repair at a step proceding DNA resynthesis. Cell. 87, 65-73 Viswanathan M, Burdett V, Baitinger C, Modrich P, Lovett ST. (2001) Redundant - 60 - exonuclease involvement in Escherichia coli methyl-directed mismatch repair. J. Biol. Chem. 276, 31053-31058 Youn CK, Kim SH, Lee DY, Song SH, Chang IY, Hyun JW, Chung MH, You HJ. (2005) Cadmium down-regulates human OGG1 through suppression of Sp1 activity. J. Biol. Chem. 280, 25185–25195 李淑貞：核酸環與鹼基配對錯誤在大腸桿菌萃取液中之共同修復。國立臺灣 大學九十學年碩士論文。 秦維璨：大腸桿菌中大型核酸環修復路徑之分析。國立台灣大學九十三學年 碩士論文 | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/33973 | - |
| dc.description.abstract | Mismatch repair（MMR）廣泛存在於生物之中，對於維持生物基因體的穩定扮演了重要的角色，其中研究最為透徹的是Escherichia coli 的
MMR，參與的蛋白包括了MutS、MutL 和MutH。正常的鹼基配對錯誤修復系統中，可將DNA 在複製時所產生的鹼基配對錯誤（mis-pairs）修復；但是當基因發生缺陷時，可能使鹼基錯誤修復系統的功能受到損害，導致修復活性下降，造成生物體內的突變率（mutation rate）提高，最後病變或死亡；然而，近幾年來有學者提出鎘、鎳是DNA 修復反應的抑制劑，進而影響修復反應進行，但其抑制的詳細機制和參與蛋白並不清楚，此外是否還有其他重金屬也會抑制鹼基配對錯誤修復系統之進行，也尚未被發現。因此我們為了要釐清重金屬對於修復反應所造成之影響，首先在in vivo 的實驗中，藉由Ames test評估鎘致突變的效應，最後發現回復突變數有相當程度的增加，因此我們懷疑鎘可能是藉由降低鹼基配對錯誤修復系統的活性，導致細菌的突變率上升；為了證實我們的推測，利用本實驗室所建構的In vitro repair assay，評估鎘、鎳抑制修復效率之程度，並且探討其他重金屬（鉛、鋅及砷）對於修復反應之影響，結果發現修復效率會隨著鎘、鎳、鉛及鋅濃度的提高而明顯的降低。為進一步得知重金屬抑制修復反應的路徑，我們利用鹼性瓊脂凝膠（Alkaline agarose gel）分析反應中所產生 之中間產物，結果發現鎘、鎳、鉛、鋅對於鹼基配對錯誤的修復，在產生斷股（nick）前即被抑制，但作用於何種修復蛋白並不清楚；因此為了解重金屬作用的目標為何，藉由在In vitro repair assay中加入鎘或鎳，再分別和具有硫氫基（sulfhydryl group，-SH）的DTT 或 -mercaptoethanol 反應後，其修復效率有明顯回升之情形。接著再分別加入十六種胺基酸一同參與試管內反應，最後發現半胱胺酸（cysteine）可以避免修復活性被鎘或鎳所抑制，因此我們推測鎘、鎳應是和修復蛋白的半胱胺酸有較強的交互作用，進而導致修復反應的進行受到阻礙。然而目前對於鎘、鎳究竟是攻擊何種修復蛋白，並且是否同樣會抑制生物體內其他的修復機制，則尚未做出定論，須待更進一步的研究與分析。 | zh_TW |
| dc.description.abstract | DNA mismatch repair (MMR) plays a major role in the recognition and correction of the mispaired bases, increasing replication fidelity and maintaining genome integrity. Except genetic factors, some of heavy metal, such as cadmium (Cd2+) and nickel (Ni2+), had been demonstrated inhibiting DNA repair activities, but the inhibitory mechanism of these metals was unclear. To understand the inhibitory activity of Cd2+ toward the prokaryotic MMR pathway, we design in vivo and in vitro experiments for study. First, we employed Ames test to study the mutagenic activity of cadmium. We found at concentration of 0.03-0.3 nM, the mutation rate increased 1.2-2.7 folds, an indication of inhibiting mismatch repair. By using a set of heteroduplexes in vitro repair assay with Escherichia coli extracts, we can directly study the changes of MMR efficiency upon exposure to cadmium or other metal ions. Our results indicated that the repair efficiency was significantly decreasing in the presence of cadmium, nickel, lead, and zinc in a dose dependent manner. Under the concentration of 0.3-0.5 mM, the repair efficiency decreased to 50% or full activity, and at 0.8 mM the repair was abolished. To investigate the inhibitory patch of these metal ions, we analyzed intermediates of limiting repair reaction by denaturing gel electrophoresis. We found that these metal ions could inhibit repair before MutH incision of the MMR process. However, reducing agents containing sulfhydryl groups (-SH), such as DTT or -mercaptoethanol, could reverse the inhibitory effect of Cd2+ or Ni2+ in a dose-dependent manner. In addition, the inhibition of Cd2+ or Ni2+ could be also overcome by cysteine. The results suggested that the progression of MMR was blocked because Cd2+and Ni2+ could directly interact with cysteine of some kinds of repairproteins. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-13T05:50:25Z (GMT). No. of bitstreams: 1 ntu-95-R93424004-1.pdf: 5224824 bytes, checksum: cb7e14b3f09c9e235ea8ba1649f03c44 (MD5) Previous issue date: 2006 | en |
| dc.description.tableofcontents | 總目次 I
圖目次 III 表目次 IV 中文摘要 i 英文摘要 ii 縮寫表 iii 前言 1 材料與方法 7 一、 菌株 7 二、 重金屬 8 三、斑點測試（Spot test） 8 四、毒性測試（Toxicity test） 9 五、沙門菌回復突變測試法（Ames test） 9 六、大腸桿菌細胞萃取液之製備 10 七、M13mp18系列雙股核酸之製備 11 八、M13mp18系列單股核酸之製備 12 九、半甲基化異雙股核酸之建構 13 十、試管中修復反應 15 十一、探針標定之方法 16 十二、抑制修復反應步驟之分析 16 十三、南方墨點分析 17 結果 18 一、鎘對於突變沙門菌之毒性分析 18 二、生物體中鎘之致突變分析 19 三、半甲基化異雙股核酸之選擇 20 四、試管中異雙股核酸之修復反應分析 20 五、重金屬對於修復效率之評估 22 六、重金屬抑制鹼基配對錯誤路徑之分析 23 (1)重金屬對於下游反應之影響 23 (2)重金屬抑制修復步驟之分析 24 七、還原劑對重金屬抑制修復反應之分析 25 八、胺基酸對重金屬抑制修復反應之分析 26 討論 27 附圖 33 附表 50 參考文獻 53 | |
| dc.language.iso | zh-TW | |
| dc.subject | 鹼基配對錯誤修復系統 | zh_TW |
| dc.subject | 重金屬 | zh_TW |
| dc.subject | Heavy metal | en |
| dc.subject | mismatch repair | en |
| dc.title | 重金屬抑制大腸桿菌核酸配對錯誤修復系統之分析 | zh_TW |
| dc.title | Analysis of Heavy Metals Inhibiting Escherichia coli Mismatch Repair System | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 94-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 高照村,蔡芷季,許濤 | |
| dc.subject.keyword | 重金屬,鹼基配對錯誤修復系統, | zh_TW |
| dc.subject.keyword | Heavy metal,mismatch repair, | en |
| dc.relation.page | 60 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2006-07-07 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 醫學檢驗暨生物技術學研究所 | zh_TW |
| 顯示於系所單位： | 醫學檢驗暨生物技術學系 | |
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