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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 許麗卿(Lih-Ching Hsu) | |
| dc.contributor.author | Bert Yu-Hung Chen | en |
| dc.contributor.author | 陳昱宏 | zh_TW |
| dc.date.accessioned | 2021-06-15T01:24:43Z | - |
| dc.date.available | 2020-08-17 | |
| dc.date.copyright | 2011-10-07 | |
| dc.date.issued | 2011 | |
| dc.date.submitted | 2011-08-16 | |
| dc.identifier.citation | Alberts B, Johnson A, Lewis J, Raff M, Roberts K, and Walter P. (2008). Molecular Biology of the Cell, 5th Edition. Garland Science, New York, USA.
Aprelikova ON, Fang BS, Meissner EG, Cotter S, Campbell M, Kuthiala A, Bessho M, Jensen RA, and Liu ET. (1999). BRCA1-Associated Growth Arrest is RB-dependent. Proceedings of the National Academy of Sciences of the United States of America, 96:11866~11871. Bae I, Rih JK, Kim HJ, Kang HJ, Hassan B, Kirilyuk A, Fan S, Avantaggiati ML, and Rosen EM. (2005). BRCA1 Regulates Gene Expression for Orderly Mitotic Progression. Cell Cycle, 4:1641~1666. Baer R, and Ludwig T. (2002). The BRCA1/BARD1 Heterodimer, a Tumor Suppressor Complex with Ubiquitin E3 Ligase Activity. Current Opinion in Genetics and Development, 12:86~91. Barford D. (1996). Molecular Mechanisms of the Protein Serine Threonine Phosphatases. Trends in Biochemical Sciences, 21:407~412. Berton TR, Matsumoto T, Page A, Conti CJ, Deng CX, Jorcano JL, and Johnson DG. (2003). Tumor Formation in Mice with Conditional Inactivation of Brca1 in Epithelial Tissues. Oncogene, 22:5415~5426. Bollen M. (2001). Combinatorial Control of Protein Phosphatase-1. Trends in Biochemical Sciences, 26:426~431. Boyle P, and Levin B, eds. (2008). World Cancer Report 2008. WHO Press, Geneva, Switzerland. Brodie SG, Xu X, Qiao W, Li WM, Cao L, and Deng CX. (2001). Multiple Genetic Changes are Associated with Mammary Tumorigenesis in Brca1 Conditional Knockout Mice. Oncogene, 20:7514~7523. Brose MS, Rebbeck TR, Calzone KA, Stopfer JE, Nathanson KL, and Weber BL. (2002). Cancer Risk Estimates for BRCA1 Mutation Carriers Identified in a Risk Evaluation Program. Journal of the National Cancer Institute, 94:1365~1372. Brzovic PS, Rajagopal P, Hoyt DW, King MC, and Klevit RE. (2001). Structure of a BRCA1-BARD1 Heterodimeric RING-RING Complex. Nature Structural Biology, 8:833~837. Calvo V, and Beato M. (2011). BRCA1 Counteracts Progesterone Action by Ubiquitination Leading to Progesterone Receptor Degradation and Epigenetic Silencing of Target Promoters. Cancer Research, 71:3422~3431. Chen Y, Farmer AA, Chen CF, Jones DC, Chen PL, and Lee WH. (1996). BRCA1 is a 220-kDa Nuclear Phosphoprotein that is Expressed and Phosphorylated in a Cell Cycle-Dependent Manner. Cancer Research, 56:3168~3172. Chen JJ, Silver D, Cantor S, Livingston DM, and Scully R. (1999). BRCA1, BRCA2, and Rad51 Operate in a Common DNA Damage Response Pathway. Cancer Research, 59:1752s~1756s. Chodosh LA. (1998). Expression of BRCA1 and BRCA2 in Normal and Neoplastic Cells. Journal of Mammary Gland Biology and Neoplasia, 3:389~402. Cohen PTW. (2002). Protein Phosphatase 1 – Targeted in Many Directions. Journal of Cell Science, 115:241~256. Cortez D, Wang Y, Qin J, and Elledge SJ. (1999). Requirement of ATM-Dependent Phosphorylation of BRCA1 in the DNA Damage Response to Double-Strand Breaks. Science, 286:1162~1166. Deng CX, and Brodie SG. (2000). Roles of BRCA1 and Its Interacting Proteins. BioEssays, 228:728~737. Deng CX. (2002). Roles of BRCA1 in Centrosome Duplication. Oncogene, 21:6222~6227. Deng CX. (2006). BRCA1: Cell Cycle Checkpoint, Genetic Instability, DNA Damage Response and Cancer Evolution. Nucleic Acids Research, 34:1416~1426. Eakin CM, MacCoss MJ, Finney GL, and Klevit RE. (2007). Estrogen Receptor a is a Putative Substrate for the BRCA1 Ubiquitin Ligase. Proceedings of the National Academy of Sciences of the United States of America, 104:5794~5799. Easton DF, Ford D, Bishop DT, and the Breast Cancer Linkage Consortium. (1995). Breast and Ovarian Cancer Incidence in BRCA1-Mutation Carriers. American Journal of Human Genetics, 56:265~271. Egloff MP, Johnson DF, Moorhead G, Cohen PTW, Cohen P, and Barford D. (1997). Structural Basis for the Recognition of Regulatory Subunits by the Catalytic Subunit of Protein Phosphatase 1. The EMBO Journal, 16:1876~1887. Fabbro M, Savage K, Hobson K, Deans AJ, Powell SN, McArthur GA, and Khanna KK. (2004). BRCA1-BARD1 Complexes are Required for p53Ser15 Phosphorylation and a G1/S Arrest Following Ionizing Radiation-Induced DNA Damage. The Journal of Biological Chemistry, 279:31251~31258. Fardilha M, Esteves SLC, Korrodi-Gregório L, da Cruz e Silva OAB, and da Cruz e Silva EF. (2010). The Physiological Relevance of Protein Phosphatase 1 and Its Interacting Proteins to Health and Disease. Current Medicinal Chemistry, 17:3996~4017. Foray N, Randrianarison V, Marot D, Perricaudet M, Lenoir G, and Feunteun J. (1999). Gamma-Rays-Induced Death of Human Cells Carrying Mutations of BRCA1 and BRCA2. Oncogene, 18:7334~7342. Gatei M, Scott SP, Filippovitch I, Soronika N, Lavin MF, Weber B, and Khanna KK. (2000). Role for ATM in DNA Damage-Induced Phosphorylation of BRCA1. Cancer Research, 60:3299~3304. Gluzman Y. (1981). SV40-Transformed Simian Cells Support the Replication of Early SV40 Mutants. Cell, 23:175~182. Gudmundsdottir K, and Ashworth A. (2006). The Roles of BRCA1 and BRCA2 and Associated Proteins in the Maintenance of Genomic Stability. Oncogene, 25:5864~5874. Hall JM, Lee MK, Newman B, Morrow JE, Anderson LA, Huey B, and King MC. (1990). Linkage of Early-Onset Familial Breast Cancer to Chromosome 17q21. Science, 250:1684~1689. Hashizume R, Fukuda M, Maeda I, Nishikawa H, Oyake D, Yabuki Y, Ogata H, and Ohta T. (2001). The RING Heterodimer BRCA1-BARD1 is a Ubiquitin Ligase Inactivated by a Breast-Cancer Derived Mutation. The Journal of Biological Chemistry, 276:14537~14540. Holt JT, Thompson ME, Szabo C, Robinson-Benion C, Arteaga CL, King MC, and Jensen RA. (1996). Growth Inhibition and Tumor Retardation by BRCA1. Nature Genetics, 12:298~302. Hsu LC, Doan TP, and White RL. (2001). Identification of a g- Tubulin-Binding Domain in BRCA1. Cancer Research, 61:7713~7718. Hsu LC. (2007). Identification and Functional Characterization of a PP1-Binding Site in BRCA1. Biochemical and Biophysical Research Communications, 360:507~512. Koonin EV, Altschul SF, and Bork P. (1996). …Functional Motifs…. Nature Genetics, 13:266~268. Lee JS, Collins KM, Brown AL, Lee CH, and Chung JH. (2000). hCds1-Mediated Phosphorylation of BRCA1 Regulates the DNA Damage Response. Nature, 404:201~204. Lee LJ, Alexander B, Schnitt SJ, Comander A, Gallagher B, Garber JE, and Tung N. (2011). Clinical Outcome of Triple Negative Breast Cancer in BRCA1 Mutation Carriers and Noncarriers. Cancer, 14:3093~3100. Liu Y, Virshup DM, White RL, and Hsu LC. (2002). Regulation of BRCA1 Phosphorylation by Interaction with Protein Phosphatase 1a. Cancer Research, 62:6357~6361. Lodish H, Berk A, Kaiser CA, Krieger M, Scott MP, Bretscher A and Ploegh H. (2008). Molecular Cell Biology, 6th Edition. W. H. Freeman, New York, USA. Lorick KL, Jensen JP, Fang S, Ong AM, Hatakeyama S, and Weissman AM. (1999). RING Fingers Mediate Ubiquitin-Conjugating Enzyme (E2)-Dependent Ubiquitination. Proceedings of the National Academy of Sciences of the United States of America, 96:11364~11369. Martin AM, and Weber BL. (2000). Genetic and Hormonal Risk Factors in Breast Cancer. Journal of the National Cancer Institute, 92:1126~1135. Matsuoka S, Rotman G, Ogawa A, Shiloh Y, Tamai K, and Elledge SJ. (2000). Ataxia Telangiectasia-Mutated Phosphorylates Chk2 in vivo and in vitro. Proceedings of the National Academy of Sciences of the United States of America, 97:10389~10394. Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W, Bell R, Rosenthal J, Hussey C, Tran T, McClure M, Frye C, Hattier T, Phelps R, Haugen-Strano A, Katcher H, Yakumo K, Gholami Z, Shaffer D, Stone S, Bayer S, Wray C, Bogden R, Dayananth P, Ward J, Tonin P, Narod S, Bristow PK, Norris FH, Helvering L, Morrison P, Rosteck P, Lai M, Barrett JC, Lewis C, Neuhausen S, Cannon-Albright L, Goldgar D, Wiseman R, Kamb A, and Skolnick MH. (1994). A Strong Candidate for the Breast and Ovarian Cancer Susceptibility Gene BRCA1. Science, 266:66~71. Pierce AJ, Johnson RD, Thompson LH, and Jasin M. (1999). XRCC3 Promotes Homology-Directed Repair of DNA Damage in Mammalian Cells. Genes & Development, 13:2633~2638. Ransburgh DJR, Chiba N, Ishioka C, Toland AE, and Parvin JD. (2010). Identification of Breast Tumor Mutations in BRCA1 that Abolish Its Function in Homologous DNA Repair. Cancer Research, 70:988~995. Ruffner H, and Verma IM. (1997). BRCA1 is a Cell Cycle-Regulated Nuclear Phosphoprotein. Proceedings of the National Academy of Sciences of the United States of America, 94:7138~7143. Ruffner H, Joazeiro CAP, Hemmati D, Hunter T, and Verma IM. (2001). Cancer-Predisposing Mutations Within the RING Domain of BRCA1: Loss of Ubiquitin Protein Ligase Activity and Protection from Radiation Hypersensitivity. Proceedings of the National Academy of Sciences of the United States of America, 98:5134~5139. Sankaran S, Crone DE, Palazzo RE, and Parvin JD. (2007). Aurora-A Kinase Regulates Breast Cancer-Associated Gene 1 Inhibition of Centrosome-Dependent Microtubule Nucleation. Cancer Research, 67:11186~11194. Scully R, Chen J, Plug A, Xiao Y, Weaver D, Feunteun J, Ashley T, and Livingston D. (1997a). Association of BRCA1 with Rad51 in Mitotic and Meiotic Cells. Cell, 88:265~275. Scully R, Chen J, Ochs RL, Keegan K, Hoekstra M, Feunteun J, and Livingston DM. (1997b). Dynamic Changes of BRCA1 Subnuclear Localization and Phosphorylation State are Initiated by DNA Damage. Cell, 90:425~435. Scully R, Ganesan S, Vlasakova K, Chen J, Socolovsky M, and Livingston DM. (1999). Genetic Analysis of BRCA1 in a Defined Tumor Cell Line. Molecular Cell, 4:1093~1099. Shen SX, Weaver Z, Xu X, Li C, Weinstein M, Chen L, Guan XY, Ried T, and Deng CX. (1998). A Targeted Disruption of the Murine Brca1 Gene Causes g-irradiation Hypersensitivity and Genetic Instability. Oncogene, 17:3115~3124. Simard J, Tonin P, Durocher F, Morgan K, Rommens J, Gingras S, Samson C, Leblanc JF, Belanger C, Dion F, Liu Q, Skolnick M, Goldgar D, Shattuck-Eidens D, Labrie F, and Narod SA. (1994). Common Origins of BRCA1 Mutations in Canadian Breast and Ovarian Cancer Families. Nature Genetics, 8:392~398. Starita LM, and Parvin JD. (2003). The Multiple Nuclear Functions of BRCA1: Transcription, Ubiquitination and DNA Repair. Current Opinion in Cell Biology, 15:345~350. Stark JM, Pierce AJ, Oh J, Pastink A, and Jasin M. (2004). Genetic Steps of Mammalian Homologous Repair with Distinct Mutagenic Consequences. Molecular and Cellular Biology, 24:9305~9316. Thakar A, Parvin JD, and Zlatanova J. (2010). BRCA1/BARD1 E3 Ubiquitin Ligase can Modify Histones H2A and H2B in the Nucleosome Particle. Journal of Biomolecular Structure and Dynamics, 27:399~405. Thakur S, Zhang HB, Peng Y, Le H, Carroll B, Ward T, Yao J, Farid LM, Couch FJ, Wilson RB, and Weber BL. (1997). Localization of BRCA1 and a Splice Variant Identifies the Nuclear Localization Signal. Molecular and Cellular Biology, 17:444~452. Thompson ME, Jensen RA, Obermiller PS, Page DL, and Holt JT. (1995). Decreased Expression of BRCA1 Accelerates Growth and is Often Present During Sporadic Breast Cancer Progression. Nature Genetics, 9:444~450. Thompson D, Easton DF, and the Breast Cancer Linkage Consortium. (2002). Cancer Incidence in BRCA1-Mutation Carriers. Journal of the National Cancer Institute, 94:1358~1365. Tibbetts RS, Cortez D, Brumbaugh KM, Scully R, Livingston D, Elledge SJ, and Abraham RT. (2000). Functional Interactions Between BRCA1 and the Checkpoint Kinase ATR During Genotoxic Stress. Genes & Development, 14:2989~3002. Tomlinson GE, Chen TTL, Stastny VA, Virmani AK, Spillman MA, Tonk V, Blum JL, Schneider NR, Wistuba II, Shay JW, Minna JD, and Gazadar AF. (1998). Characterization of a Breast Cancer Cell Line Derived from a Germ-Line BRCA1 Mutation Carrier. Cancer Research, 58:3237~3242. Vaughn JP, Davis PL, Jarboe MD, Huper G, Evans AC, Wiseman RW, Berchuck A, Iglehart JD, Futreal PA, and Marks JR. (1996). BRCA1 Expression is Induced Before DNA Synthesis in Both Normal and Tumor-Derived Breast Cells. Cell Growth & Differentiation, 7:711~715. Wang HC, Chou WC, Shieh SY, and Shen CY. (2006). Ataxia Telangiectasia mutated and Checkpoint Kinase 2 Regulate BRCA1 to Promote the Fidelity of DNA End-Joining. Cancer Research, 66:1391~1400. Wilson CA, Ramos L, Villaseñor MR, Anders KH, Press MF, Clarke K, Karlan B, Chen JJ, Scully R, Livingston D, Zuch RH, Kanter MH, Cohen S, Calzone FJ, and Slamon DJ. (1999). Localization of Human BRCA1 and Its Loss in High-Grade, Non-Inherited Breast Carcinomas. Nature Genetics, 21:236~240. Winter SL, Bosnoyan-Collins L, Pinnaduwage D, and Andrulis IL. (2007). The Interaction of PP1 with BRCA1 and Analysis of Their Expression in Breast Tumors. BMC Cancer, 7:85. Wu LC, Wang ZW, Tsan JT, Spillman MA, Phung A, Xu XL, Yang MCW, Hwang LY, Bowcock AM, and Baer R. (1996). Identification of a RING Protein that can Interact in vivo with the BRCA1 Gene Product. Nature Genetics, 14:430~440. Wu J, Huen MSY, Lu LY, Ye L, Dou Y, Ljungman M, Chen J, and Yu X. (2009). Histone Ubiquitination Associates with BRCA1-Dependent DNA Damage Response. Molecular and Cellular Biology, 29:849~860. Wu J, Lu LY, and Yu X. (2010). The Role of BRCA1 in DNA Damage Response. Protein Cell, 1:117~123. Xu B, Kim ST, and Kastan MB. (2001a). Involvement of BRCA1 in S-Phase and G2-Phase Checkpoints After Ionizing Irradiation. Molecular and Cellular Biology, 21:3445~3450. Xu X, Qiao W, Linke SP, Liu C, Li WM, Furth PA, Harris CC, and Deng CX. (2001b). Genetic Interactions Between Tumor Suppressors BRCA1 and p53 in Apoptosis, Cell Cycle and Tumorigenesis. Nature Genetics, 28:266~271. Xu B, O’Donnell AH, Kim ST, and Kastan MB. (2002). Phosphorylation of Serine 1387 in BRCA1 is Specifically Required for the ATM-Mediated S-Phase Checkpoint After Ionizing Irradiation. Cancer Research, 62:4588~4591. Yarden RI, Pardo-Reoyo S, Sgagias M, Cowan KH, and Brody LC. (2002). BRCA1 Regulates the G2/M Checkpoint by Activating Chk1 Kinase upon DNA Damage. Nature Genetics, 30:285~289. Yoshikawa K, Honda K, Inamoto T, Shinohara H, Yamauchi A, Suga K, Okuyama T, Shimada T, Kodama H, Noguchi S, Gazdar AF, Yamaoka Y, and Takahashi R. (1999). Reduction of BRCA1 Protein Expression in Japanese Sporadic Breast Carcinomas and Its Frequent Loss in BRCA1-Associated Cancers. Clinical Cancer Research, 5:1249~1261. Yu X, and Baer R. (2000). Nuclear Localization and Cell-Specific Expression of CtIP, a Protein that Associates with the BRCA1 Tumor Suppressor. The Journal of Biological Chemistry, 275:18541~18549. Zhang J, Willers H, Feng Z, Ghosh JC, Kim S, Weaver DT, Chung JH, Powell SN, and Xia F. (2004). Chk2 Phosphorylation of BRCA1 Regulates DNA Double-Strand Break Repair. Molecular and Cellular Biology, 24:708~718. Zhong Q, Chen CF, Li S, Chen Y, Wang CC, Xiao J, Chen PL, Sharp ZD, and Lee WH. (1999). Association of BRCA1 with the hRad50-hMre11-p95 Complex and the DNA Damage Response. Science, 285:747~750. Zhuang J, Zhang J, Willers H, Wang H, Chung JH, van Gent DC, Hallahan DE, Powell SN, and Xia F. (2006). Checkpoint Kinase 2-Mediated Phosphorylation of BRCA1Regulates the Fidelity of Nonhomologous End-Joining. Cancer Research, 66:1401~1408. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/42820 | - |
| dc.description.abstract | 目前已知抗乳癌基因BRCA1會透過[RK]-x(0,1)-[VI]-x-[FW]這個第一型磷酸水解酶PP1共同結合基序與PP1進行互動，結合位點在BRCA1的898~901殘基之間，序列為898KVTF901。 先前的研究顯示改造而得的突變F901A會消除BRCA1與PP1之間的結合，並會干擾由BRCA1調節的DNA損傷訊息傳導與修復機制。 剔除整個KVTF序列也被發現會引起類似的表型，顯示BRCA1與PP1的結合對於BRCA1的正常運作具有重要的意義。 有趣的是，乳癌信息中心資料庫列有一個K898E突變，原先是在亞甚肯納茲猶太裔的患者身上被發現。 我們試著檢視這個突變對於BRCA1-PP1結合能力以及BRCA1所調節的DNA損傷反應機制之影響。 我們的結果顯示BRCA1K898E和PP1之間的結合能力顯著降低，且BRCA1K898E也無法減輕缺乏BRCA1的細胞對於游離輻射的高敏感性，同時這些細胞也被觀察到在接受游離輻射後DNA修復機制有所不足。 免疫染色分析更顯示缺乏BRCA1的細胞以BRCA1K898E重組之後，在接受游離輻射後的Rad51焦點形成能力明顯的低於以野生型BRCA1重組的細胞。 綜合這些結果可以發現PP1結合基序的完整性對於PP1和BRCA1的結合非常重要；PP1和BRCA1的互動也對於BRCA1所調節的DNA修復機制扮演關鍵的調控角色。 這也顯示BRCA1和PP1的結合與互動有機會發展為癌症治療的生物標記或藥物標靶。 | zh_TW |
| dc.description.abstract | BRCA1 is known to bind and interact with PP1 through an [RK]-x(0,1)-[VI]-x-[FW] PP1-binding consensus motif located at residues 898~901 of the BRCA1 protein, with the sequence 898KVTF901. Previous studies have shown that an engineered F901A mutation can abolish binding between BRCA1 and PP1, and disrupt BRCA1-mediated DNA damage signaling and repair. Deletion of the entire KVTF sequence was also found to induce a similar phenotype, suggesting that the binding interaction between BRCA1 and PP1 is critical for the normal functioning of BRCA1. Interestingly, the Breast Cancer Information Core database lists a K898E mutation, originally identified in a patient of Ashkenazi Jewish descent. We sought to examine the impact of this mutation upon BRCA1-PP1 binding and the BRCA1-mediated DNA damage response. Our results demonstrated that binding between BRCA1K898E and PP1 was significantly reduced. Furthermore, BRCA1K898E was unable to mitigate IR hypersensitivity in BRCA1-deficient cells, and inadequate post-IR DNA repair was also observed. Immunostaining analysis revealed that BRCA1-deficient cells reconstituted with BRCA1K898E had significantly lower rates of Rad51 foci formation post-IR, as compared to cells reconstituted with wild-type BRCA1. Taken together, these results indicate that the integrity of the PP1-binding motif is crucial for the binding interaction between PP1 and BRCA1, which in turn plays a key role in regulating BRCA1-mediated DNA repair. This suggests that the BRCA1-PP1 binding interaction may have potential as a biomarker and therapeutic target for the treatment of cancer. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T01:24:43Z (GMT). No. of bitstreams: 1 ntu-100-R98423011-1.pdf: 4400951 bytes, checksum: 2e7cf0543741c86e6776695a557f2cfc (MD5) Previous issue date: 2011 | en |
| dc.description.tableofcontents | Master Thesis Certification by the Oral Defense Committee i
Acknowledgements ii 中文摘要 iii Abstract iv Table of Contents v List of Figures vii List of Tables viii List of Abbreviations ix I. Introduction 1 I-1 BRCA1 1 I-2 The BRCA1-BARD1 E3 Ubiquitin Ligase 3 I-3 BRCA1 and the Cell Cycle 3 I-4 The Role of BRCA1 in the DNA Damage Response 6 I-5 Clinical Significance of BRCA1 Mutations 8 I-6 BRCA1 and PP1 9 II. Research Significance and Objectives 16 III. Experimental Procedures 19 III-1 Vector Construction 19 III-2 Cell Lines 20 III-3 Cell Culture and Transfection 20 III-4 SDS-PAGE and Western Analysis 21 III-5 GST Pull-down Assay 21 III. Experimental Procedures (cont’d) 19 III-6 Coimmunoprecipitation Assay 22 III-7 Colony Formation Assay 23 III-8 Comet Assay 23 III-9 Rad51 Foci Formation Assay 24 III-10 Generation of BRCA1 Stable Clones 25 III-11 Generation of pDR-GFP Stable Clones 26 III-12 Statistical Analysis 27 III-13 Lab Solutions 27 III-14 Research Tools and Databases 30 IV. Results 32 IV-1 The K898 Residue is Highly Conserved in BRCA1 32 IV-2 The K898E Mutation Disrupts Binding Between BRCA1 and PP1 32 IV-3 BRCA1K898E Cannot Mitigate IR Hypersensitivity in BRCA1-deficient Cells 32 IV-4 DNA Repair is Defective in BRCA1K898E Transfectants 34 IV-5 Post-IR Rad51 Foci Formation is Impaired in BRCA1K898E Transfectants 36 IV-6 Successful Generation of BRCA1 Wild-type and Mutant Stable Clones 37 IV-7 Successful Generation of pDR-GFP Stable Clones 37 V. Discussion 47 V-1 The Role of PP1 in BRCA1-Mediated DNA Repair 47 V-2 Exploring the Underlying Mechanisms of BRCA1K898E Dysfunction 47 V-3 Potential Paths from the Bench to the Bedside 49 VI. Conclusion 51 References 52 | |
| dc.language.iso | en | |
| dc.subject | BRCA1 | zh_TW |
| dc.subject | 乳癌 | zh_TW |
| dc.subject | DNA修復 | zh_TW |
| dc.subject | Rad51 | zh_TW |
| dc.subject | PP1 | zh_TW |
| dc.subject | PP1 | en |
| dc.subject | breast cancer | en |
| dc.subject | DNA repair | en |
| dc.subject | Rad51 | en |
| dc.subject | BRCA1 | en |
| dc.title | 位於抗乳癌基因BRCA1的蛋白質磷酸水解酶結合位點之臨床相關突變會干擾DNA修復機制 | zh_TW |
| dc.title | A Clinically Relevant Mutation in the PP1-Binding Motif of BRCA1 Disrupts DNA Repair | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 99-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 周綠蘋(Lu-Ping Chow),李財坤(Tsai-Kun Li),孔繁璐(Fan-Lu Kung) | |
| dc.subject.keyword | BRCA1,PP1,Rad51,DNA修復,乳癌, | zh_TW |
| dc.subject.keyword | BRCA1,PP1,Rad51,DNA repair,breast cancer, | en |
| dc.relation.page | 61 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2011-08-16 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 藥學研究所 | zh_TW |
| 顯示於系所單位： | 藥學系 | |
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