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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 李弘文(Hung-Wen Li) | |
| dc.contributor.author | Kuan-Chi Wang | en |
| dc.contributor.author | 王冠期 | zh_TW |
| dc.date.accessioned | 2022-11-23T09:14:51Z | - |
| dc.date.available | 2021-08-06 | |
| dc.date.available | 2022-11-23T09:14:51Z | - |
| dc.date.copyright | 2021-08-06 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-08-04 | |
| dc.identifier.citation | 1 Ishikawa-Ankerhold, H. C., Ankerhold, R. Drummen, G. P. Advanced fluorescence microscopy techniques—Frap, Flip, Flap, Fret and Flim. Molecules 17, 4047-4132 (2012). 2 Yusufzai, T. Kadonaga, J. T. Annealing helicase 2 (AH2), a DNA-rewinding motor with an HNH motif. Proceedings Of The National Academy Of Sciences Of America 107, 20970-20973 (2010). 3 Burnham, D. R. et al. Annealing helicase HARP closes RPA-stabilized DNA bubbles non-processively. Nucleic Acids Research 45, 4687-4695 (2017). 4 Shin, S., Hyun, K., Kim, J. Hohng, S. ATP binding to Rad5 initiates replication fork reversal by inducing the unwinding of the leading arm and the formation of the Holliday junction. Cell Reports 23, 1831-1839 (2018). 5 Manosas, M., Perumal, S. K., Croquette, V. Benkovic, S. J. Direct observation of stalled fork restart via fork regression in the T4 replication system. Science 338, 1217-1220 (2012). 6 Ciccia, A. Elledge, S. J. The DNA damage response: making it safe to play with knives. Molecular Cell 40, 179-204 (2010). 7 Tye, S., Ronson, G. E. Morris, J. R. in Seminars In Cell Developmental Biology. (Elsevier). 8 Poole, L. A. Cortez, D. Functions of SMARCAL1, ZRANB3, and HLTF in maintaining genome stability. Critical Reviews In Biochemistry and Molecular Biology 52, 696-714 (2017). 9 Yusufzai, T. Kadonaga, J. T. HARP is an ATP-driven annealing helicase. Science 322, 748-750 (2008). 10 Chavez, D. A., Greer, B. H. Eichman, B. F. The HIRAN domain of helicase-like transcription factor positions the DNA translocase motor to drive efficient DNA fork regression. Journal Of Biological Chemistry 293, 8484-8494 (2018). 11 Kile, A. C. et al. HLTF’s ancient HIRAN domain binds 3′ DNA ends to drive replication fork reversal. Molecular Cell 58, 1090-1100 (2015). 12 Achar, Y. J. et al. Human HLTF mediates postreplication repair by its HIRAN domain-dependent replication fork remodelling. Nucleic Acids Research 43, 10277-10291 (2015). 13 Rothenberg, E., Grimme, J. M., Spies, M. Ha, T. Human Rad52-mediated homology search and annealing occurs by continuous interactions between overlapping nucleoprotein complexes. Proceedings Of The National Academy Of Sciences Of America 105, 20274-20279 (2008). 14 Badu-Nkansah, A., Mason, A. C., Eichman, B. F. Cortez, D. Identification of a substrate recognition domain in the replication stress response protein zinc finger ran-binding domain-containing protein 3 (ZRANB3). Journal Of Biological Chemistry 291, 8251-8257 (2016). 15 Marians, K. J. Lesion bypass and the reactivation of stalled replication forks. Annual Review Of Biochemistry 87, 217-238 (2018). 16 Mayle, R. et al. Mcm10 has potent strand-annealing activity and limits translocase-mediated fork regression. Proceedings Of The National Academy Of Sciences Of America 116, 798-803 (2019). 17 Halder, S. et al. Mechanism of Replication Fork Reversal and Protection by Human RAD51 and RAD51 Paralogs. Available at SSRN 3742313. 18 Liao, H., Ji, F., Helleday, T. Ying, S. Mechanisms for stalled replication fork stabilization: new targets for synthetic lethality strategies in cancer treatments. EMBO Reports 19, e46263 (2018). 19 Mason, J. M., Chan, Y.-L., Weichselbaum, R. W. Bishop, D. K. Non-enzymatic roles of human RAD51 at stalled replication forks. Nature Communications 10, 1-11 (2019). 20 Berti, M., Cortez, D. Lopes, M. The plasticity of DNA replication forks in response to clinically relevant genotoxic stress. Nature Reviews Molecular Cell Biology 21, 633-651 (2020). 21 Ciccia, A. et al. Polyubiquitinated PCNA recruits the ZRANB3 translocase to maintain genomic integrity after replication stress. Molecular Cell 47, 396-409 (2012). 22 Saada, A. A., Lambert, S. A. Carr, A. M. Preserving replication fork integrity and competence via the homologous recombination pathway. DNA Repair 71, 135-147 (2018). 23 Zellweger, R. et al. Rad51-mediated replication fork reversal is a global response to genotoxic treatments in human cells. Journal Of Cell Biology 208, 563-579 (2015). 24 Robu, M. E., Inman, R. B. Cox, M. M. RecA protein promotes the regression of stalled replication forks in vitro. Proceedings Of The National Academy Of Sciences Of America 98, 8211-8218 (2001). 25 Michel, B., Sinha, A. K. Leach, D. R. Replication fork breakage and restart in Escherichia coli. Microbiology And Molecular Biology Reviews: MMBR 82 (2018). 26 Weaver, G. M., Mettrick, K. A., Corocher, T. A., Graham, A. Grainge, I. Replication fork collapse at a protein‐DNA roadblock leads to fork reversal, promoted by the RecQ helicase. Molecular Microbiology 111, 455-472 (2019). 27 Atkinson, J. McGlynn, P. Replication fork reversal and the maintenance of genome stability. Nucleic Acids Research 37, 3475-3492 (2009). 28 Neelsen, K. J. Lopes, M. Replication fork reversal in eukaryotes: from dead end to dynamic response. Nature Reviews Molecular Cell Biology 16, 207-220 (2015). 29 Mijic, S. et al. Replication fork reversal triggers fork degradation in BRCA2-defective cells. Nature Communications 8, 1-11 (2017). 30 Quinet, A., Lemaçon, D. Vindigni, A. Replication fork reversal: players and guardians. Molecular Cell 68, 830-833 (2017). 31 Heller, R. C. Marians, K. J. Replisome assembly and the direct restart of stalled replication forks. Nature Reviews Molecular Cell Biology 7, 932-943 (2006). 32 Taglialatela, A. et al. Restoration of replication fork stability in BRCA1-and BRCA2-deficient cells by inactivation of SNF2-family fork remodelers. Molecular Cell 68, 414-430. e418 (2017). 33 Blastyák, A., Hajdú, I., Unk, I. Haracska, L. Role of double-stranded DNA translocase activity of human HLTF in replication of damaged DNA. Molecular And Cellular Biology 30, 684 (2010). 34 Bhat, K. P. Cortez, D. RPA and RAD51: fork reversal, fork protection, and genome stability. Nature Structural Molecular Biology 25, 446-453 (2018). 35 Bétous, R. et al. SMARCAL1 catalyzes fork regression and Holliday junction migration to maintain genome stability during DNA replication. Genes Development 26, 151-162 (2012). 36 Sebesta, M., Cooper, C. D., Ariza, A., Carnie, C. J. Ahel, D. Structural insights into the function of ZRANB3 in replication stress response. Nature Communications 8, 1-16 (2017). 37 Bétous, R. et al. Substrate-selective repair and restart of replication forks by DNA translocases. Cell Reports 3, 1958-1969 (2013). 38 Liu, W., Krishnamoorthy, A., Zhao, R. Cortez, D. Two replication fork remodeling pathways generate nuclease substrates for distinct fork protection factors. Science Advances 6, eabc3598 (2020). 39 Thakar, T. et al. Ubiquitinated-PCNA protects replication forks from DNA2-mediated degradation by regulating Okazaki fragment maturation and chromatin assembly. Nature Communications 11, 1-14 (2020). 40 Ciccia, A. et al. The ZRANB3 translocase associates with poly-ubiquitinated PCNA to promote fork restart and limit recombination after replication stress. Molecular Cell 47, 396 (2012). 41 Ray Chaudhuri, A. et al. Topoisomerase I poisoning results in PARP-mediated replication fork reversal. Nature Structural Molecular Biology 19, 417-423, (2012). 42 Motegi, A. et al. Polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH prevents genomic instability from stalled replication forks. Proceedings Of The National Academy Of Sciences Of America 105, 12411-12416 (2008). 43 Peng, M. et al. Opposing roles of FANCJ and HLTF protect forks and restrain replication during stress. Cell Reports 24, 3251-3261 (2018). 44 Zeman, M. K. Cimprich, K. A. Causes and consequences of replication stress. Nature Cell Biology 16, 2-9 (2014). | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/79875 | - |
| dc.description.abstract | "進行 DNA 複製過程中，損傷的DNA 模板會導致 DNA 複製叉停滯。人體反轉複製叉酵素 (SMARCAL1、ZRANB3、HLTF) 可將停滯的 DNA 複製叉，轉換成雞爪形狀之反轉複製叉，以保護複製叉結構及增加 DNA 穩定性，為細胞爭取時間修復受損的 DNA。反轉複製叉形成過程包括兩條新生股與原先模板股解除配對，兩條模板股相互配對，隨後新生股相互配對，以形成四股 DNA 交叉。然而目前對於反轉複製叉酵素如何催化複製叉反轉機制，仍尚未釐清，本論文利用生化方法與單分子螢光共振能量轉移技術，探討反轉複製叉酵素的作用機制。通過單分子螢光共振能量轉移實驗，我們驗證了三種人類反轉複製叉酵素皆可以有效地進行反轉複製叉反應，且作用速率相似。接著，利用生化解旋酶實驗發現三種反轉複製叉酵素皆具有解旋酶特性，可將 DNA 兩股分離，但各自特性不同: SMARCAL1 僅能解旋母股，而 ZRANB3, HLTF 能夠解旋前進與延遲股。利用 DNA 兩股的生化黏合實驗中不互補序列在不同的複製叉位點，發現 SMARCAL1 與 ZRANB3, HLTF 利用不同黏合機制，SMARCAL1 無法跨越位於三股 DNA 交叉的損傷位點，然而 ZRANB3 與 HLTF的反應性卻不受阻； ZRANB3 與 HLTF 黏合機制類似但卻有不同的序列不互補忍受度，這些結果讓我們定義出這些反轉複製叉酵素的特性，並為這些反轉複製叉酵素的作用機制提出基本的生化模型。" | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-23T09:14:51Z (GMT). No. of bitstreams: 1 U0001-0108202115581000.pdf: 4485577 bytes, checksum: 2bc92f94671cd65c0c4fb305f0b22f1a (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | "目錄 謝誌 ⅲ 摘要 ⅳ Abstract ⅴ 目錄 ⅵ 圖目錄 ⅷ 表目錄 ⅸ 第一章 緒論 1 1-1 複製叉反轉 (Replication fork reversal) 1 1-2 SMARCAL1, ZRANB3, HLTF蛋白序列、結構及功能 3 1-3 研究動機 6 第二章 實驗方法與設計 9 2-1 蛋白質來源 9 2-2 核酸基質設計 9 2-3 溶液配方與製備 23 2-4 反應玻片製備 25 2-5 實驗流程 26 2-6 數據分析 29 第三章 實驗結果與討論 31 3-1 單分子螢光共振能量轉移實驗觀察反轉複製叉酵素的反應速率 31 3-2 反轉複製叉酵素 ZRANB3 與 HLTF 具有解旋酶特性 39 3-3 反轉複製叉酵素的黏合活性 51 第四章 實驗總結與未來展望 59 4-1 實驗總結 59 4-2 未來展望 67 參考文獻 68 附錄 72" | |
| dc.language.iso | zh-TW | |
| dc.subject | 單分子螢光共振能量轉移螢光共振能量轉移 | zh_TW |
| dc.subject | 複製叉反轉 | zh_TW |
| dc.subject | 解旋酶 | zh_TW |
| dc.subject | SMARCAL1 | zh_TW |
| dc.subject | ZRANB3 | zh_TW |
| dc.subject | HLTF | zh_TW |
| dc.subject | helicase | en |
| dc.subject | ZRANB3 | en |
| dc.subject | SMARCAL1 | en |
| dc.subject | reverse fork | en |
| dc.subject | single molecule FRET | en |
| dc.subject | HLTF | en |
| dc.title | 利用生物物理與生化分析方法探討反轉複製叉家族蛋白於跨越 DNA 損傷的作用機制 | zh_TW |
| dc.title | Biophysical and Biochemical Approaches on How Fork Reversal Enzymes Function in DNA Lesion Bypass Mechanism | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 冀宏源(Hsin-Tsai Liu),廖泓鈞(Chih-Yang Tseng),詹迺立,林敬哲 | |
| dc.subject.keyword | 複製叉反轉,解旋酶,SMARCAL1,ZRANB3,HLTF,單分子螢光共振能量轉移螢光共振能量轉移, | zh_TW |
| dc.subject.keyword | reverse fork,helicase,SMARCAL1,ZRANB3,HLTF,single molecule FRET, | en |
| dc.relation.page | 77 | |
| dc.identifier.doi | 10.6342/NTU202101974 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2021-08-04 | |
| dc.contributor.author-college | 理學院 | zh_TW |
| dc.contributor.author-dept | 化學研究所 | zh_TW |
| 顯示於系所單位： | 化學系 | |
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