請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/7888完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 鄧述諄(Shu-Chun Teng) | |
| dc.contributor.author | Pin-Yu Wang | en |
| dc.contributor.author | 王品瑀 | zh_TW |
| dc.date.accessioned | 2021-05-19T17:57:24Z | - |
| dc.date.available | 2021-08-26 | |
| dc.date.available | 2021-05-19T17:57:24Z | - |
| dc.date.copyright | 2016-08-26 | |
| dc.date.issued | 2016 | |
| dc.date.submitted | 2016-08-15 | |
| dc.identifier.citation | Albert, M., and Helin, K. (2010). Histone methyltransferases in cancer. Semin Cell Dev Biol 21, 209-220.
Bekker-Jensen, S., Lukas, C., Melander, F., Bartek, J., and Lukas, J. (2005). Dynamic assembly and sustained retention of 53BP1 at the sites of DNA damage are controlled by Mdc1/NFBD1. J Cell Biol 170, 201-211. Bishop, A.J.R., and Schiestl, R.H. (2002). Homologous Recombination and Its Role in Carcinogenesis. Journal of Biomedicine and Biotechnology 2:2, 75–85. Cebria, F., Kobayashi, C., Umesono, Y., Nakazawa, M., Mineta, K., Ikeo, K., Gojobori, T., Itoh, M., Taira, M., Sanchez Alvarado, A., et al. (2002). FGFR-related gene nou-darake restricts brain tissues to the head region of planarians. Nature 419, 620-624. Chapman, J.R., and Jackson, S.P. (2008). Phospho-dependent interactions between NBS1 and MDC1 mediate chromatin retention of the MRN complex at sites of DNA damage. EMBO Rep 9, 795-801. Choudhury, A.D., Xu, H., and Baer, R. (2004). Ubiquitination and proteasomal degradation of the BRCA1 tumor suppressor is regulated during cell cycle progression. J Biol Chem 279, 33909-33918. Cock-Rada, A.M., Medjkane, S., Janski, N., Yousfi, N., Perichon, M., Chaussepied, M., Chluba, J., Langsley, G., and Weitzman, J.B. (2012). SMYD3 promotes cancer invasion by epigenetic upregulation of the metalloproteinase MMP-9. Cancer Res 72, 810-820. Dome`nec Farre ́, Roma` Roset, Mario Huerta, Jose ́ E. Adsuara, Llorenc ̧ Rosello ́, M. Mar Alba` , and Messeguer, X. (2003). Identification of patterns in biological sequences at the ALGGEN server PROMO and MALGEN. Nucleic Acids Research 31, 3651-3653. Escribano-Diaz, C., Orthwein, A., Fradet-Turcotte, A., Xing, M., Young, J.T., Tkac, J., Cook, M.A., Rosebrock, A.P., Munro, M., Canny, M.D., et al. (2013). A cell cycle-dependent regulatory circuit composed of 53BP1-RIF1 and BRCA1-CtIP controls DNA repair pathway choice. Mol Cell 49, 872-883. Foreman, K.W., Brown, M., Park, F., Emtage, S., Harriss, J., Das, C., Zhu, L., Crew, A., Arnold, L., Shaaban, S., et al. (2011). Structural and functional profiling of the human histone methyltransferase SMYD3. PLoS One 6, e22290. Hamamoto, R., Furukawa, Y., Morita, M., Iimura, Y., Silva, F.P., Li, M., Yagyu, R., and Nakamura, Y. (2004). SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells. Nat Cell Biol 6, 731-740. Hamamoto, R., Silva, F.P., Tsuge, M., Nishidate, T., Katagiri, T., Nakamura, Y., and Furukawa, Y. (2006). Enhanced SMYD3 expression is essential for the growth of breast cancer cells. Cancer Sci 97, 113-118. Heyer, W.D., Ehmsen, K.T., and Liu, J. (2010). Regulation of homologous recombination in eukaryotes. Annu Rev Genet 44, 113-139. Huen, M.S., and Chen, J. (2008). The DNA damage response pathways: at the crossroad of protein modifications. Cell Res 18, 8-16. Hunt, C.R., Ramnarain, D., Horikoshi, N., Iyengar, P., Pandita, R.K., Shay, J.W., and Pandita, T.K. (2013). Histone modifications and DNA double-strand break repair after exposure to ionizing radiations. Radiat Res 179, 383-392. Kim, H., Heo, K., Kim, J.H., Kim, K., Choi, J., and An, W. (2009). Requirement of histone methyltransferase SMYD3 for estrogen receptor-mediated transcription. J Biol Chem 284, 19867-19877. Kim, J.M., Kim, K., Schmidt, T., Punj, V., Tucker, H., Rice, J.C., Ulmer, T.S., and An, W. (2015). Cooperation between SMYD3 and PC4 drives a distinct transcriptional program in cancer cells. Nucleic Acids Res 43, 8868-8883. Kolas NK, Chapman JR, Nakada S, Y.J., Chahwan R, Sweeney FD, Panier S, Mendez M, Wildenhain J, Thomson TM, Pelletier L, et al. (2007). Orchestration of the DNA-Damage Response by the RNF8 Ubiquitin Ligase. Science 318(5856), 1637-1640. Kunizaki, M., Hamamoto, R., Silva, F.P., Yamaguchi, K., Nagayasu, T., Shibuya, M., Nakamura, Y., and Furukawa, Y. (2007). The lysine 831 of vascular endothelial growth factor receptor 1 is a novel target of methylation by SMYD3. Cancer Res 67, 10759-10765. Liu, C., Fang, X., Ge, Z., Jalink, M., Kyo, S., Bjorkholm, M., Gruber, A., Sjoberg, J., and Xu, D. (2007). The telomerase reverse transcriptase (hTERT) gene is a direct target of the histone methyltransferase SMYD3. Cancer Res 67, 2626-2631. Mailand, N., Bekker-Jensen, S., Faustrup, H., Melander, F., Bartek, J., Lukas, C., and Lukas, J. (2007). RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins. Cell 131, 887-900. Martin, C., and Zhang, Y. (2005). The diverse functions of histone lysine methylation. Nat Rev Mol Cell Biol 6, 838-849. Mason, J.M., Dusad, K., Wright, W.D., Grubb, J., Budke, B., Heyer, W.D., Connell, P.P., Weichselbaum, R.R., and Bishop, D.K. (2015). RAD54 family translocases counter genotoxic effects of RAD51 in human tumor cells. Nucleic Acids Res 43, 3180-3196. Mattiroli, F., Vissers, J.H., van Dijk, W.J., Ikpa, P., Citterio, E., Vermeulen, W., Marteijn, J.A., and Sixma, T.K. (2012). RNF168 ubiquitinates K13-15 on H2A/H2AX to drive DNA damage signaling. Cell 150, 1182-1195. Mazur, P.K., Reynoird, N., Khatri, P., Jansen, P.W., Wilkinson, A.W., Liu, S., Barbash, O., Van Aller, G.S., Huddleston, M., Dhanak, D., et al. (2014). SMYD3 links lysine methylation of MAP3K2 to Ras-driven cancer. Nature 510, 283-287. Minter-Dykhouse, K., Ward, I., Huen, M.S., Chen, J., and Lou, Z. (2008). Distinct versus overlapping functions of MDC1 and 53BP1 in DNA damage response and tumorigenesis. J Cell Biol 181, 727-735. Nimonkar AV, O.A., Genschel J, Modrich P, Kowalczykowski SC (2008). Human exonuclease 1 and BLM helicase interact to resect DNA and initiate DNA repair. Proc Natl Acad Sci U S A 105(44), 16906-16911. Panier, S., and Boulton, S.J. (2014). Double-strand break repair: 53BP1 comes into focus. Nat Rev Mol Cell Biol 15, 7-18. Pierce, A.J., Johnson, R.D., Thompson, L.H., and Jasin, M. (1999). XRCC3 promotes homology-directed repair of DNA damage in mammalian cells. GENES & DEVELOPMENT 13(20), 2633-2638. Podhorecka, M., Skladanowski, A., and Bozko, P. (2010). H2AX Phosphorylation: Its Role in DNA Damage Response and Cancer Therapy. J Nucleic Acids 2010. Robert J. Sims 3rd, and Reinberg, D. (2004). From chromatin to cancer a new histone lysine methyltransferase enters the mix. Nature Cell Biology 6, 685-687. Sartori, A.A., Lukas, C., Coates, J., Mistrik, M., Fu, S., Bartek, J., Baer, R., Lukas, J., and Jackson, S.P. (2007). Human CtIP promotes DNA end resection. Nature 450, 509-514. Shi, W., Ma, Z., Willers, H., Akhtar, K., Scott, S.P., Zhang, J., Powell, S., and Zhang, J. (2008). Disassembly of MDC1 foci is controlled by ubiquitin-proteasome-dependent degradation. J Biol Chem 283, 31608-31616. Shun-Fu Tseng, Chun-Yu Chang, Kou-Juey Wu, and Teng, S.-C. (2005). Importin KPNA2 Is Required for Proper Nuclear Localization and Multiple Functions of NBS1. The Journal of Biological Chemistry 280, 39594-39600. Stucki, M., Clapperton, J.A., Mohammad, D., Yaffe, M.B., Smerdon, S.J., and Jackson, S.P. (2005). MDC1 directly binds phosphorylated histone H2AX to regulate cellular responses to DNA double-strand breaks. Cell 123, 1213-1226. Stucki, M., and Jackson, S.P. (2004). MDC1/NFBD1: a key regulator of the DNA damage response in higher eukaryotes. DNA Repair (Amst) 3, 953-957. Symington, L.S., and Gautier, J. (2011). Double-strand break end resection and repair pathway choice. Annu Rev Genet 45, 247-271. Thorslund, T., McIlwraith, M.J., Compton, S.A., Lekomtsev, S., Petronczki, M., Griffith, J.D., and West, S.C. (2010). The breast cancer tumor suppressor BRCA2 promotes the specific targeting of RAD51 to single-stranded DNA. Nat Struct Mol Biol 17, 1263-1265. Tomimatsu, N., Mukherjee, B., Catherine Hardebeck, M., Ilcheva, M., Vanessa Camacho, C., Louise Harris, J., Porteus, M., Llorente, B., Khanna, K.K., and Burma, S. (2014). Phosphorylation of EXO1 by CDKs 1 and 2 regulates DNA end resection and repair pathway choice. Nat Commun 5, 3561. Tran, P.T., Erdeniz, N., Symington, L.S., and Liskay, R.M. (2004). EXO1-A multi-tasking eukaryotic nuclease. DNA Repair (Amst) 3, 1549-1559. Van Aller, G.S., Reynoird, N., Barbash, O., Huddleston, M., Liu, S., Zmoos, A.F., McDevitt, P., Sinnamon, R., Le, B., Mas, G., et al. (2012). Smyd3 regulates cancer cell phenotypes and catalyzes histone H4 lysine 5 methylation. Epigenetics 7, 340-343. Wilson, K.A., and Stern, D.F. (2008). NFBD1/MDC1, 53BP1 and BRCA1 have both redundant and unique roles in the ATM pathway. Cell Cycle 7, 3584-3594. Zhang, J., Ma, Z., Treszezamsky, A., and Powell, S.N. (2005). MDC1 interacts with Rad51 and facilitates homologous recombination. Nat Struct Mol Biol 12, 902-909. Zhenkun Lou, Claudia Christiano Silva Chini, Katherine Minter-Dykhouse, and Chen, J. (2003a). MDC1 Regulates BRCA1 Localization and Phosphorylation in DNA Damage Checkpoint Control. J Biol Chem 278(16), 13599-13602. Zhenkun Lou, Claudia Christiano Silva Chini, Katherine Minter-Dykhouse, and Chen, J. (2003b). Mediator of DNA damage checkpoint protein 1 regulates BRCA1 localization and phosphorylation in DNA damage checkpoint control. J Biol Chem 278, 13599-13602. Zou, J.N., Wang, S.Z., Yang, J.S., Luo, X.G., Xie, J.H., and Xi, T. (2009). Knockdown of SMYD3 by RNA interference down-regulates c-Met expression and inhibits cells migration and invasion induced by HGF. Cancer Lett 280, 78-85. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/7888 | - |
| dc.description.abstract | SMYD3在腫瘤形成中為常見的致癌基因。癌症中，過度表現的SMYD3與細胞增殖和較差的預後有關聯。在這篇研究中，我們發現SMYD3會調控DNA 修復。 在microarray 和ChIP-seq結果顯示SMYD3會活化MDC1、EXO1和RAD54B等與同源重組相關的基因表現。SMYD3的缺乏會使細胞對DNA損傷較敏感，而且同源重組的修復機制也會產生缺陷。在缺乏SMYD3的細胞中-H2A.X foci存在的時間延長，而 MDC1與BRCA1 foci的形成減少。而且，當SMYD3被抑制時，在MDC1、 EXO1和RAD54B啟動子處H3K4me3的量也會跟著減少。總結，我們發現SMYD3藉由調控 MDC1、 EXO1和 RAD54B的表現進而影響同源重組修復的能力。 | zh_TW |
| dc.description.abstract | SMYD3 emerges as a common oncogene in tumorigenesis, and overexpression of SMYD3 is linked to increased cell proliferation and poor prognosis in human cancers. Here we show that SMYD3 regulates DNA repair. ChIP-seq and microarray analyses demonstrate that SMYD3 binds and activates homologous recombination genes (MDC1, EXO1, and RAD54B) in MCF7 cells. SMYD3-depleted cells became hypersensitive to DNA damage and were defective in homologous recombination repair. Retention of -H2A.X foci and decrease of MDC1 and BRCA1 foci were observed in SMYD3 knockdown cells. Moreover, depletion of SMYD3 inhibited H3K4 trimethylation on MDC1, EXO1, and RAD54B promoter. Together, we discover a novel mechanism of SMYD3 in homologous recombination by regulating the expression of MDC1, EXO1, and RAD54B. | en |
| dc.description.provenance | Made available in DSpace on 2021-05-19T17:57:24Z (GMT). No. of bitstreams: 1 ntu-105-R03445114-1.pdf: 3465896 bytes, checksum: 14eda2c4846c7123ed48ccfa15903031 (MD5) Previous issue date: 2016 | en |
| dc.description.tableofcontents | 口試委員會審定書
誌謝………………………………………………………………………………… i 中文摘要…………………………………………………………………………...... ii ABSTRACT.…………………………………………………………………………. iii CONTENTS…………………………………………………………………………. iv INTRODUCTION…………………………………………………………………... 1 RESULTS……………………………………………………………………………. 5 Loss of SMYD3 results in decreased expression of DNA repair genes SMYD3 plays a role in homologous recombination repair Inhibition of SMYD3 postpones the DNA repair Loss of SMYD3 impairs formation of BRCA1 foci through regulating expression of MDC1 The establishment of H3K4 trimethylation on HR genes promoter is SMYD3-dependent DISCUSSION ………………………………………………………………………. 10 MATERIALS AND METHODS………………………………………………….... 13 Cell culture and genes knockdown Immunoblotting and antibodies RNA purification and quantitative reverse transcription PCR Homologous recombination activity assay Plasmid end-joining assay Immunofluorescence staining Colony formation assay Chromatin immunoprecipitation Nuclear/cytosol fractionation FIGURES……………………………………………………………………………. 19 CONTRIBUTION TABLE…………………………………………………………. 34 REFERENCES……………………………………………………………………… 35 | |
| dc.language.iso | en | |
| dc.title | 探討SMYD3在同源重組中扮演的角色 | zh_TW |
| dc.title | Characterization of the Roles of SMYD3 in Homologous Recombination | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 104-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 李財坤,李明學 | |
| dc.subject.keyword | SMYD3,同源重組,DNA 修復, | zh_TW |
| dc.subject.keyword | SMYD3,Homologous recombination,DNA repair, | en |
| dc.relation.page | 37 | |
| dc.identifier.doi | 10.6342/NTU201602684 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2016-08-15 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 微生物學研究所 | zh_TW |
| 顯示於系所單位： | 微生物學科所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-105-1.pdf | 3.38 MB | Adobe PDF | 檢視/開啟 |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。