請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/20505
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 林敬哲(Jing-Jer Lin) | |
dc.contributor.author | Hsin-Ru Chan | en |
dc.contributor.author | 詹炘儒 | zh_TW |
dc.date.accessioned | 2021-06-08T02:51:05Z | - |
dc.date.copyright | 2017-09-14 | |
dc.date.issued | 2017 | |
dc.date.submitted | 2017-08-15 | |
dc.identifier.citation | 1. Allsopp, R.C., Vaziri, H., Patterson, C., Goldstein, S., Younglai, E.V., Futcher, A.B., Greider, C.W., and Harley, C.B. (1992). Telomere length predicts replicative capacity of human fibroblasts. Proc Natl Acad Sci U S A 89, 10114-10118.
2. Arora, R., Lee, Y., Wischnewski, H., Brun, C.M., Schwarz, T., and Azzalin, C.M. (2014). RNaseH1 regulates TERRA-telomeric DNA hybrids and telomere maintenance in ALT tumour cells. Nat Commun 5, 5220. 3. Azzalin, C.M., and Lingner, J. (2008). Telomeres: the silence is broken. Cell Cycle 7, 1161-1165. 4. Azzalin, C.M., Reichenbach, P., Khoriauli, L., Giulotto, E., and Lingner, J. (2007). Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends. Science 318, 798-801. 5. Bah, A., Wischnewski, H., Shchepachev, V., and Azzalin, C.M. (2012). The telomeric transcriptome of Schizosaccharomyces pombe. Nucleic Acids Res 40, 2995-3005. 6. Balk, B., Maicher, A., Dees, M., Klermund, J., Luke-Glaser, S., Bender, K., and Luke, B. (2013). Telomeric RNA-DNA hybrids affect telomere-length dynamics and senescence. Nat Struct Mol Biol 20, 1199-1205. 7. Bodnar, A.G., Ouellette, M., Frolkis, M., Holt, S.E., Chiu, C.P., Morin, G.B., Harley, C.B., Shay, J.W., Lichtsteiner, S., and Wright, W.E. (1998). Extension of life-span by introduction of telomerase into normal human cells. Science 279, 349-352. 8. Boguslawski, S. J., Smith, D. E., Michalak, M. A., Mickelson, K. E., Yehle, C. O, Patterson, W. L., and Carrico, R. J. (1986). Characterization of monoclonal antibody to DNA.RNA and its application to immunodetection of hybrids. J Immunol Methods 89, 123-30. 9. Bower, K., Napier, C.E., Cole, S.L., Dagg, R.A., Lau, L.M., Duncan, E.L., Moy, E.L., and Reddel, R.R. (2012). Loss of wild-type ATRX expression in somatic cell hybrids segregates with activation of Alternative Lengthening of Telomeres. PLoS One 7, e50062. 10. Brewster, N.K., Johnston, G.C., and Singer, R.A. (2001). A bipartite yeast SSRP1 analog comprised of Pob3 and Nhp6 proteins modulates transcription. Mol Cell Biol 21, 3491-3502. 11. Bryan, T.M., Englezou, A., Dalla-Pozza, L., Dunham, M.A., and Reddel, R.R. (1997). Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines. Nat Med 3, 1271-1274. 12. Bryan, T.M., Englezou, A., Gupta, J., Bacchetti, S., and Reddel, R.R. (1995). Telomere elongation in immortal human cells without detectable telomerase activity. EMBO J 14, 4240-4248. 13. Budd, M. E., and Campbell, J. L. (1997). A yeast replicative helicase, Dna2 helicase, interacts with yeast FEN-1 nuclease in carrying out its essential function. Mol Cell Biol 17, 2136-2142. 14. Castellano-Pozo, M., Santos-Pereira, J.M., Rondon, A.G., Barroso, S., Andujar, E., Perez-Alegre, M., Garcia-Muse, T., and Aguilera, A. (2013). R loops are linked to histone H3 S10 phosphorylation and chromatin condensation. Mol Cell 52, 583-590. 15. Chan, C.S., and Tye, B.K. (1983). A family of Saccharomyces cerevisiae repetitive autonomously replicating sequences that have very similar genomic environments. J Mol Biol 168, 505-523. 16. Chawla, R., and Azzalin, C.M. (2008). The telomeric transcriptome and SMG proteins at the crossroads. Cytogenet Genome Res 122, 194-201. 17. Chiarle, R., Zhang, Y., Frock, R.L., Lewis, S.M., Molinie, B., Ho, Y.J., Myers, D.R., Choi, V.W., Compagno, M., Malkin, D.J. (2011). Genome-wide translocation sequencing reveals mechanisms of chromosome breaks and rearrangements in B cells. Cell 147, 107-119. 18. Cook, G.P., Tomlinson, I.M., Walter, G., Riethman, H., Carter, N.P., Buluwela, L., Winter, G., and Rabbitts, T.H. (1994). A map of the human immunoglobulin VH locus completed by analysis of the telomeric region of chromosome 14q. Nat Genet 7, 162-168. 19. Counter, C.M., Meyerson, M., Eaton, E.N., and Weinberg, R.A. (1997). The catalytic subunit of yeast telomerase. Proc Natl Acad Sci U S A 94, 9202-9207. 20. de Laat, W.L., Appeldoorn, E., Jaspers, N.G., and Hoeijmakers, J.H. (1998). DNA structural elements required for ERCC1-XPF endonuclease activity. J Biol Chem 273, 7835-7842. 21. Deng, Z., Norseen, J., Wiedmer, A., Riethman, H., and Lieberman, P.M. (2009). TERRA RNA binding to TRF2 facilitates heterochromatin formation and ORC recruitment at telomeres. Mol Cell 35, 403-413. 22. Dianov, G., and Lindahl, T. (1994). Reconstitution of the DNA base excision-repair pathway. Curr Biol 4, 1069-1076. 23. Doe, C.L., Ahn, J.S., Dixon, J., and Whitby, M.C. (2002). Mus81-Eme1 and Rqh1 involvement in processing stalled and collapsed replication forks. J Biol Chem 277, 32753-32759. 24. Duquette, M.L., Handa, P., Vincent, J.A., Taylor, A.F., and Maizels, N. (2004). Intracellular transcription of G-rich DNAs induces formation of G-loops, novel structures containing G4 DNA. Genes Dev 18, 1618-1629. 25. Entian, K.D., Schuster, T., Hegemann, J.H., Becher, D., Feldmann, H., Guldener, U., Gotz, R., Hansen, M., Hollenberg, C.P., Jansen, G. (1999). Functional analysis of 150 deletion mutants in Saccharomyces cerevisiae by a systematic approach. Mol Gen Genet 262, 683-702. 26. Erie, D.A. (2002). The many conformational states of RNA polymerase elongation complexes and their roles in the regulation of transcription. Biochim Biophys Acta 1577, 224-239. 27. Evans, S.K., and Lundblad, V. (1999). Est1 and Cdc13 as comediators of telomerase access. Science 286, 117-120. 28. Fiorentini, P., Huang, K. N., Tishkoff, D. X., Kolodner, R. D., and Symington, L. S. (1997). Exonuclease I of Saccharomyces cerevisiae functions in mitotic recombination in vivo and in vitro. Mol Cell Biol 17, 2764-2773. 29. Gall,J.G. (1995) Beginning of the end: origins of the telomere. In Telomeres. Blackbur, E.H. and Greider, C.W. (eds.), Cold Spring Harbor Laboratory Press, New York, pp. 1-10 30. Gary, R., Park, M. S., Nolan, J. P., Cornelius, H. L., Kozyreva, O. G., Tran, H. T., Lobachev, K. S., Resnick, M. A., and Gordenin, D. A. (1999). Mol Cell Biol 19, 5373-5382 31. Ginno, P.A., Lott, P.L., Christensen, H.C., Korf, I., and Chedin, F. (2012). R-loop formation is a distinctive characteristic of unmethylated human CpG island promoters. Mol Cell 45, 814-825. 32. Gomez-Gonzalez, B., Felipe-Abrio, I., and Aguilera, A. (2009). The S-phase checkpoint is required to respond to R-loops accumulated in THO mutants. Mol Cell Biol 29, 5203-5213. 33. Gottipati, P., Cassel, T.N., Savolainen, L., and Helleday, T. (2008). Transcription-associated recombination is dependent on replication in Mammalian cells. Mol Cell Biol 28, 154-164. 34. Greider, C.W., and Blackburn, E.H. (1985). Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 43, 405-413. 35. Groh, M., and Gromak, N. (2014). Out of balance: R-loops in human disease. PLoS Genet 10, e1004630. 36. Harley, C.B., Futcher, A.B., and Greider, C.W. (1990). Telomeres shorten during ageing of human fibroblasts. Nature 345, 458-460. 37. Harrington, J.J., and Lieber, M.R. (1994). Functional domains within FEN-1 and RAD2 define a family of structure-specific endonucleases: implications for nucleotide excision repair. Genes Dev 8, 1344-1355. 38. Hartzog, G.A., Wada, T., Handa, H., and Winston, F. (1998). Evidence that Spt4, Spt5, and Spt6 control transcription elongation by RNA polymerase II in Saccharomyces cerevisiae. Genes Dev 12, 357-369. 39. Hastie, N.D., Dempster, M., Dunlop, M.G., Thompson, A.M., Green, D.K., and Allshire, R.C. (1990). Telomere reduction in human colorectal carcinoma and with ageing. Nature 346, 866-868. 40. Hayflick, L., Moorhead, P.S. (1961). The serial cultivation of human diploid cell strains. Exp Cell Res 25:585-621. 41. Heaphy, C.M., de Wilde, R.F., Jiao, Y., Klein, A.P., Edil, B.H., Shi, C., Bettegowda, C., Rodriguez, F.J., Eberhart, C.G., Hebbar, S. (2011). Altered telomeres in tumors with ATRX and DAXX mutations. Science 333, 425. 42. Herrera-Moyano, E., Mergui, X., Garcia-Rubio, M.L., Barroso, S., and Aguilera, A. (2014). The yeast and human FACT chromatin-reorganizing complexes solve R-loop-mediated transcription-replication conflicts. Genes Dev 28, 735-748. 43. Hraiky, C., Raymond, M.A., and Drolet, M. (2000). RNase H overproduction corrects a defect at the level of transcription elongation during rRNA synthesis in the absence of DNA topoisomerase I in Escherichia coli. J Biol Chem 275, 11257-11263. 44. Huertas, P., and Aguilera, A. (2003). Cotranscriptionally formed DNA:RNA hybrids mediate transcription elongation impairment and transcription-associated recombination. Mol Cell 12, 711-721. 45. Itoh, T., and Tomizawa, J. (1980). Formation of an RNA primer for initiation of replication of ColE1 DNA by ribonuclease H. Proc Natl Acad Sci U S A 77, 2450-2454. 46. Jansen, L.E., den Dulk, H., Brouns, R.M., de Ruijter, M., Brandsma, J.A., and Brouwer, J. (2000). Spt4 modulates Rad26 requirement in transcription-coupled nucleotide excision repair. EMBO J 19, 6498-6507. 47. Kang, M.J., Lee, C.H., Kang, Y.H., Cho, I.T., Nguyen, T.A., and Seo, Y.S. (2010). Genetic and functional interactions between Mus81-Mms4 and Rad27. Nucleic Acids Res 38, 7611-7625. 48. Kang, Y.H., Kang, M.J., Kim, J.H., Lee, C.H., Cho, I.T., Hurwitz, J., and Seo, Y.S. (2009). The MPH1 gene of Saccharomyces cerevisiae functions in Okazaki fragment processing. J Biol Chem 284, 10376-10386. 49. Kim, N.W., Piatyszek, M.A., Prowse, K.R., Harley, C.B., West, M.D., Ho, P.L., Coviello, G.M., Wright, W.E., Weinrich, S.L., and Shay, J.W. (1994). Specific association of human telomerase activity with immortal cells and cancer. Science 266, 2011-2015. 50. Kruger, W., and Herskowitz, I. (1991). A negative regulator of HO transcription, SIN1 (SPT2), is a nonspecific DNA-binding protein related to HMG1. Mol Cell Biol 11, 4135-4146. 51. Le, S., Moore, J.K., Haber, J.E., and Greider, C.W. (1999). RAD50 and RAD51 define two pathways that collaborate to maintain telomeres in the absence of telomerase. Genetics 152, 143-152. 52. Lendvay, T.S., Morris, D.K., Sah, J., Balasubramanian, B., and Lundblad, V. (1996). Senescence mutants of Saccharomyces cerevisiae with a defect in telomere replication identify three additional EST genes. Genetics 144, 1399-1412. 53. Li, X., and Manley, J.L. (2006). Cotranscriptional processes and their influence on genome stability. Genes Dev 20, 1838-1847. 54. Lin, J.J., and Zakian, V.A. (1996). The Saccharomyces CDC13 protein is a single-strand TG1-3 telomeric DNA-binding protein in vitro that affects telomere behavior in vivo. Proc Natl Acad Sci U S A 93, 13760-13765. 55. Lin, W., Sampathi, S., Dai, H., Liu, C., Zhou, M., Hu, J., Chai, W., and Shen, B. (2013). Mammalian DNA2 helicase/nuclease cleaves G-quadruplex DNA and is required for telomere integrity. EMBO J 32, 1425-1439. 56. Linardopoulou, E., Mefford, H.C., Nguyen, O., Friedman, C., van den Engh, G., Farwell, D.G., Coltrera, M., and Trask, B.J. (2001). Transcriptional activity of multiple copies of a subtelomerically located olfactory receptor gene that is polymorphic in number and location. Hum Mol Genet 10, 2373-2383. 57. Lindstrom, D.L., and Hartzog, G.A. (2001). Genetic interactions of Spt4-Spt5 and TFIIS with the RNA polymerase II CTD and CTD modifying enzymes in Saccharomyces cerevisiae. Genetics 159, 487-497. 58. Lingner, J., Hughes, T.R., Shevchenko, A., Mann, M., Lundblad, V., and Cech, T.R. (1997). Reverse transcriptase motifs in the catalytic subunit of telomerase. Science 276, 561-567. 59. Lo, A.W., Sabatier, L., Fouladi, B., Pottier, G., Ricoul, M., and Murnane, J.P. (2002). DNA amplification by breakage/fusion/bridge cycles initiated by spontaneous telomere loss in a human cancer cell line. Neoplasia 4, 531-538. 60. Luke, B., Panza, A., Redon, S., Iglesias, N., Li, Z., and Lingner, J. (2008). The Rat1p 5' to 3' exonuclease degrades telomeric repeat-containing RNA and promotes telomere elongation in Saccharomyces cerevisiae. Mol Cell 32, 465-477. 61. Lundblad, V., and Blackburn, E.H. (1993). An alternative pathway for yeast telomere maintenance rescues est1- senescence. Cell 73, 347-360. 62. Lundblad, V., and Szostak, J.W. (1989). A mutant with a defect in telomere elongation leads to senescence in yeast. Cell 57, 633-643. 63. Mazon, G., and Symington, L.S. (2013). Mph1 and Mus81-Mms4 prevent aberrant processing of mitotic recombination intermediates. Mol Cell 52, 63-74. 64. McEachern, M.J., and Blackburn, E.H. (1994). A conserved sequence motif within the exceptionally diverse telomeric sequences of budding yeasts. Proc Natl Acad Sci U S A 91, 3453-3457. 65. Mischo, H.E., Gomez-Gonzalez, B., Grzechnik, P., Rondon, A.G., Wei, W., Steinmetz, L., Aguilera, A., and Proudfoot, N.J. (2011). Yeast Sen1 helicase protects the genome from transcription-associated instability. Mol Cell 41, 21-32. 66. Moyzis, R.K., Buckingham, J.M., Cram, L.S., Dani, M., Deaven, L.L., Jones, M.D., Meyne, J., Ratliff, R.L., and Wu, J.R. (1988). A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. Proc Natl Acad Sci U S A 85, 6622-6626. 67. Munashingha, P. R., Lee, C. H., Kang, Y. H., Shin, Y. K., Nguyen, T. A., and Seo, Y. S. (2012). The trans-autostimulatory activity of Rad27 suppresses dna2 defects in Okazaki fragment processing. J Biol Chem 287, 8675-8687. 68. Napier, C.E., Huschtscha, L.I., Harvey, A., Bower, K., Noble, J.R., Hendrickson, E.A., and Reddel, R.R. (2015). ATRX represses alternative lengthening of telomeres. Oncotarget 6, 16543-16558. 69. Ng, L.J., Cropley, J.E., Pickett, H.A., Reddel, R.R., and Suter, C.M. (2009). Telomerase activity is associated with an increase in DNA methylation at the proximal subtelomere and a reduction in telomeric transcription. Nucleic Acids Res 37, 1152-1159. 70. Nguyen, H. D., Yadav, T., Giri, S., Saez, B., Graubert, T. A., and Zou, L. (2017). Functions of replication protein A as a sensor of R loops and a regulator of RNaseH1. Mol Cell 65, 832-847. 71. Nourani, A., Robert, F., and Winston, F. (2006). Evidence that Spt2/Sin1, an HMG-like factor, plays roles in transcription elongation, chromatin structure, and genome stability in Saccharomyces cerevisiae. Mol Cell Biol 26, 1496-1509. 72. Nugent, C.I., Hughes, T.R., Lue, N.F., and Lundblad, V. (1996). Cdc13p: a single-strand telomeric DNA-binding protein with a dual role in yeast telomere maintenance. Science 274, 249-252. 73. Olovnikov, A.M. (1973). A theory of marginotomy. The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon. J Theor Biol 41, 181-190. 74. Osman, F., Dixon, J., Doe, C.L., and Whitby, M.C. (2003). Generating crossovers by resolution of nicked Holliday junctions: a role for Mus81-Eme1 in meiosis. Mol Cell 12, 761-774. 75. Parenteau, J., and Wellinger, R.J. (1999). Accumulation of single-stranded DNA and destabilization of telomeric repeats in yeast mutant strains carrying a deletion of RAD27. Mol Cell Biol 19, 4143-4152. 76. Parenteau, J., and Wellinger, R.J. (2002). Differential processing of leading- and lagging-strand ends at Saccharomyces cerevisiae telomeres revealed by the absence of Rad27p nuclease. Genetics 162, 1583-1594. 77. Peterson, C.L., Kruger, W., and Herskowitz, I. (1991). A functional interaction between the C-terminal domain of RNA polymerase II and the negative regulator SIN1. Cell 64, 1135-1143. 78. Pfeiffer, V., Crittin, J., Grolimund, L., and Lingner, J. (2013). The THO complex component Thp2 counteracts telomeric R-loops and telomere shortening. EMBO J 32, 2861-2871. 79. Pfeiffer, V., and Lingner, J. (2012). TERRA promotes telomere shortening through exonuclease 1-mediated resection of chromosome ends. PLoS Genet 8, e1002747. 80. Polak, P., and Arndt, P.F. (2008). Transcription induces strand-specific mutations at the 5' end of human genes. Genome Res 18, 1216-1223. 81. Prado, F., and Aguilera, A. (2005). Impairment of replication fork progression mediates RNA polII transcription-associated recombination. EMBO J 24, 1267-1276. 82. Qiu, J., Qian, Y., Frank, P., Wintersberger, U., and Shen, B. (1999). Saccharomyces cerevisiae RNase H(35) functions in RNA primer removal during lagging-strand DNA synthesis, most efficiently in cooperation with Rad27 nuclease. Mol Cell Biol 19, 8361-8371. 83. Reddel, R.R., Bryan, T.M., and Murnane, J.P. (1997). Immortalized cells with no detectable telomerase activity. A review. Biochemistry (Mosc) 62, 1254-1262. 84. Redon, S., Reichenbach, P., and Lingner, J. (2010). The non-coding RNA TERRA is a natural ligand and direct inhibitor of human telomerase. Nucleic Acids Res 38, 5797-5806. 85. Riethman, H.C., Xiang, Z., Paul, S., Morse, E., Hu, X.L., Flint, J., Chi, H.C., Grady, D.L., and Moyzis, R.K. (2001). Integration of telomere sequences with the draft human genome sequence. Nature 409, 948-951. 86. Rizki, A., and Lundblad, V. (2001). Defects in mismatch repair promote telomerase-independent proliferation. Nature 411, 713-716. 87. Roy, D., and Lieber, M.R. (2009). G clustering is important for the initiation of transcription-induced R-loops in vitro, whereas high G density without clustering is sufficient thereafter. Mol Cell Biol 29, 3124-3133. 88. Roy, D., Zhang, Z., Lu, Z., Hsieh, C.L., and Lieber, M.R. (2010). Competition between the RNA transcript and the nontemplate DNA strand during R-loop formation in vitro: a nick can serve as a strong R-loop initiation site. Mol Cell Biol 30, 146-159. 89. Rudolph, C., Fleck, O., and Kohli, J. (1998). Schizosaccharomyces pombe exo1 is involved in the same mismatch repair pathway as msh2 and pms1. Curr Genet 34, 343-350. 90. Schlesinger, M.B., and Formosa, T. (2000). POB3 is required for both transcription and replication in the yeast Saccharomyces cerevisiae. Genetics 155, 1593-1606. 91. Schoeftner, S., and Blasco, M.A. (2008). Developmentally regulated transcription of mammalian telomeres by DNA-dependent RNA polymerase II. Nat Cell Biol 10, 228-236. 92. Shampay, J., Szostak, J.W., and Blackburn, E.H. (1984). DNA sequences of telomeres maintained in yeast. Nature 310, 154-157. 93. Shay, J.W. (2013). Are short telomeres predictive of advanced cancer? Cancer Discov 3, 1096-1098. 94. Shay, J.W., and Bacchetti, S. (1997). A survey of telomerase activity in human cancer. Eur J Cancer 33, 787-791. 95. Shilatifard, A., Conaway, R.C., and Conaway, J.W. (2003). The RNA polymerase II elongation complex. Annu Rev Biochem 72, 693-715. 96. Sikdar, N., Banerjee, S., Zhang, H., Smith, S., and Myung, K. (2008). Spt2p defines a new transcription-dependent gross chromosomal rearrangement pathway. PLoS Genet 4, e1000290. 97. Singer, M.S., and Gottschling, D.E. (1994). TLC1: template RNA component of Saccharomyces cerevisiae telomerase. Science 266, 404-409. 98. Skourti-Stathaki, K., Proudfoot, N.J., and Gromak, N. (2011). Human senataxin resolves RNA/DNA hybrids formed at transcriptional pause sites to promote Xrn2-dependent termination. Mol Cell 42, 794-805. 99. Smith, J.R., and Pereira-Smith, O.M. (1996). Replicative senescence: implications for in vivo aging and tumor suppression. Science 273, 63-67. 100. Sollier, J., Stork, C.T., Garcia-Rubio, M.L., Paulsen, R.D., Aguilera, A., and Cimprich, K.A. (2014). Transcription-coupled nucleotide excision repair factors promote R-loop-induced genome instability. Mol Cell 56, 777-785. 101. Staresincic, L., Fagbemi, A.F., Enzlin, J.H., Gourdin, A.M., Wijgers, N., Dunand-Sauthier, I., Giglia-Mari, G., Clarkson, S.G., Vermeulen, W., and Scharer, O.D. (2009). Coordination of dual incision and repair synthesis in human nucleotide excision repair. EMBO J 28, 1111-1120. 102. Stavenhagen, J.B., and Zakian, V.A. (1994). Internal tracts of telomeric DNA act as silencers in Saccharomyces cerevisiae. Genes Dev 8, 1411-1422. 103. Stirling, P.C., Chan, Y.A., Minaker, S.W., Aristizabal, M.J., Barrett, I., Sipahimalani, P., Kobor, M.S., and Hieter, P. (2012). R-loop-mediated genome instability in mRNA cleavage and polyadenylation mutants. Genes Dev 26, 163-175. 104. Teng, S.C., Chang, J., McCowan, B., and Zakian, V.A. (2000). Telomerase-independent lengthening of yeast telomeres occurs by an abrupt Rad50p-dependent, Rif-inhibited recombinational process. Mol Cell 6, 947-952. 105. Teng, S.C., and Zakian, V.A. (1999). Telomere-telomere recombination is an efficient bypass pathway for telomere maintenance in Saccharomyces cerevisiae. Mol Cell Biol 19, 8083-8093. 106. Teasley, D. C., Parajuli, S., Nguyen, M., Moore, H. R., Alspach, E., Lock, Y. J., Honaker, Y., Saharia, A., Piwnica-Worms, H., and Stewart, S. A. (2015). Flap endonuclease 1 limits telomere fragility on the leading strand. J Biol Chem 290, 15133-15145. 107. Thomas, M., White, R.L., and Davis, R.W. (1976). Hybridization of RNA to double-stranded DNA: formation of R-loops. Proc Natl Acad Sci U S A 73, 2294-2298. 108. Tous, C., and Aguilera, A. (2007). Impairment of transcription elongation by R-loops in vitro. Biochem Biophys Res Commun 360, 428-432. 109. Tran, P. T., Erdeniz, N., Dudley, S., and Liskay, R. M. (2002). Characterization of nuclease-dependent functions of Exo1p in Saccharomyces cerevisiae. DNA Repair 1, 895-912 110. Trask, B.J., Friedman, C., Martin-Gallardo, A., Rowen, L., Akinbami, C., Blankenship, J., Collins, C., Giorgi, D., Iadonato, S., Johnson, F. (1998). Members of the olfactory receptor gene family are contained in large blocks of DNA duplicated polymorphically near the ends of human chromosomes. Hum Mol Genet 7, 13-26. 111. Tsubouchi, H., and Ogawa, H. (2000). Exo1 roles for repair of DNA double-strand breaks and meiotic crossing over in Saccharomyces cerevisiae. Mol Biol Cell 11, 2221-2233. 112. Tuduri, S., Crabbe, L., Conti, C., Tourriere, H., Holtgreve-Grez, H., Jauch, A., Pantesco, V., De Vos, J., Thomas, A., Theillet, C. (2009). Topoisomerase I suppresses genomic instability by preventing interference between replication and transcription. Nat Cell Biol 11, 1315-1324. 113. Turchi, J.J., Huang, L., Murante, R.S., Kim, Y., and Bambara, R.A. (1994). Enzymatic completion of mammalian lagging-strand DNA replication. Proc Natl Acad Sci U S A 91, 9803-9807. 114. Vallen, E.A., and Cross, F.R. (1995). Mutations in RAD27 define a potential link between G1 cyclins and DNA replication. Mol Cell Biol 15, 4291-4302. 115. Virta-Pearlman, V., Morris, D.K., and Lundblad, V. (1996). Est1 has the properties of a single-stranded telomere end-binding protein. Genes Dev 10, 3094-3104. 116. Vodenicharov, M. D., Laterreur, N., and Wellinger, R. J. (2010). Telomere capping in non-dividing yeast cells requires Yku and Rap1. EMBO J, 29, 3007-3019 117. Wada, T., Takagi, T., Yamaguchi, Y., Ferdous, A., Imai, T., Hirose, S., Sugimoto, S., Yano, K., Hartzog, G.A., Winston, F. (1998). DSIF, a novel transcription elongation factor that regulates RNA polymerase II processivity, is composed of human Spt4 and Spt5 homologs. Genes Dev 12, 343-356. 118. Wahba, L., Amon, J.D., Koshland, D., and Vuica-Ross, M. (2011). RNase H and multiple RNA biogenesis factors cooperate to prevent RNA:DNA hybrids from generating genome instability. Mol Cell 44, 978-988. 119. Walmsley, R.W., Chan, C.S., Tye, B.K., and Petes, T.D. (1984). Unusual DNA sequences associated with the ends of yeast chromosomes. Nature 310, 157-160. 120. Watson, J.D. (1972). Origin of concatemeric T7 DNA. Nat New Biol 239, 197-201. 121. Wellinger, R.E., Prado, F., and Aguilera, A. (2006). Replication fork progression is impaired by transcription in hyperrecombinant yeast cells lacking a functional THO complex. Mol Cell Biol 26, 3327-3334. 122. Xu, B., and Clayton, D.A. (1996). RNA-DNA hybrid formation at the human mitochondrial heavy-strand origin ceases at replication start sites: an implication for RNA-DNA hybrids serving as primers. EMBO J 15, 3135-3143. 123. Yamada, M., Hayatsu, N., Matsuura, A., and Ishikawa, F. (1998). Y'-Help1, a DNA helicase encoded by the yeast subtelomeric Y' element, is induced in survivors defective for telomerase. J Biol Chem 273, 33360-33366. 124. Yan, Z., Delannoy, M., Ling, C., Daee, D., Osman, F., Muniandy, P.A., Shen, X., Oostra, A.B., Du, H., Steltenpool, J. (2010). A histone-fold complex and FANCM form a conserved DNA-remodeling complex to maintain genome stability. Mol Cell 37, 865-878. 125. Yehezkel, S., Segev, Y., Viegas-Pequignot, E., Skorecki, K., and Selig, S. (2008). Hypomethylation of subtelomeric regions in ICF syndrome is associated with abnormally short telomeres and enhanced transcription from telomeric regions. Hum Mol Genet 17, 2776-2789. 126. Yu, K., Chedin, F., Hsieh, C.L., Wilson, T.E., and Lieber, M.R. (2003). R-loops at immunoglobulin class switch regions in the chromosomes of stimulated B cells. Nat Immunol 4, 442-451. 127. Yu, T.Y., Kao, Y.W., and Lin, J.J. (2014). Telomeric transcripts stimulate telomere recombination to suppress senescence in cells lacking telomerase. Proc Natl Acad Sci U S A 111, 3377-3382. 128. Zakian, V.A. (1995). Telomeres: beginning to understand the end. Science 270, 1601-1607. 129. Zhang, L.F., Ogawa, Y., Ahn, J.Y., Namekawa, S.H., Silva, S.S., and Lee, J.T. (2009). Telomeric RNAs mark sex chromosomes in stem cells. Genetics 182, 685-698. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/20505 | - |
dc.description.abstract | 端粒是位於染色體末端特殊的核蛋白結構,其功能在於阻止染色體末端遭受核酸酶降解、避免染色體末端融合,並且防止染色體不正常的修復和重組。在酵母菌Saccharomyces cerevisiae中,其端粒是由長度250至300鹼基對、TG1-3/C1-3A的重複性序列所組成,在正常狀況下,酵母菌藉由端粒酶維持端粒的長度,端粒酶是由一條 RNA與蛋白質次單元組成的複合體,其利用RNA作為合成端粒序列的模板,再用反轉錄酶的活性合成新的端粒DNA序列,然而在失去端粒酶活性的酵母菌中,端粒會隨著複製次數增加而逐漸縮短,接著進入老化階段(senescence),此時有一群的酵母菌能夠藉由一種稱為端粒重組(telomere recombination)的方式維持端粒長度,撐過senescence而存活下來,這與人類癌細胞使用ALT (alternative lengthening of telomeres)維持端粒長度的方式非常相似,然而目前對於端粒重組的機制仍不甚清楚。在我們先前的研究發現一種稱為TERRA的telomeric long noncoding RNA會參與在端粒重組的過程中,TERRA RNA和端粒DNA形成RNA:DNA hybrid,在端粒酶缺失的酵母菌中TERRA會促使端粒重組的發生,因此我們想近一步探討TERRA到底是如何引發端粒重組的發生。利用基因剔除的技術我們發現參與在nucleotide excision repair、RNA polymerase regulation和chromatin remodeling pathway的基因對於端粒重組的發生影響不大,然而當剔除5' flap endonuclease RAD27基因後發現端粒重組提早發生,而且過量表現RNase H能夠抑制端粒重組提早發生的現象,顯示rad27 deletion所造成的端粒重組異常可能和TERRA有關。接著我們發現短片段端粒DNA會大量累積在rad27 deletion的酵母菌中,而過量表現5'-3' exonuclease/flap-endonuclease EXO1能抑制rad27 deletion所造成的端粒重組異常。接著利用偵測total TERRA level和DNA-IP的方式觀察到rad27 deletion會造成TERRA累積在端粒,顯示Rad27可能參與在處理TERRA結構的過程中,於是我們利用生化分析的方式將Rad27蛋白和R-loop結構在in vitro條件下進行反應,從初步結果發現Rad27可以切R-loop結構,但Rad27D179A endonuclease dead mutants無法切R-loop結構。這些結果顯示Rad27可能具有切除TERRA並調控端粒重組的新功能。結合以上結果和目前已知rad27 mutants導致人類細胞癌化以及遺傳性疾病的發生,我們的研究賦予Rad27在端粒重組甚至疾病致病機轉一個全新的角色。 | zh_TW |
dc.description.abstract | Telomeres are nucleoprotein structures located at both ends of eukaryotic linear chromosomes, which protect chromosome ends from nucleolytic degradation, inter-chromosomal fusion, and unnecessary repair-recombination. In Saccharomyces cerevisiae, the telomeric DNA are 250-300 base pairs TG1-3/C1-3A repetitive sequences. In general condition, the telomere length of S. cerevisiae is maintained by a ribonucleoprotein (RNP) called telomerase, which uses its RNA component to synthesize new telomeric DNA. However, in S. cerevisiae lacking telomerase, a recombination-based mechanism is used to maintain telomere length, which is similar to alternative lengthening of telomeres (ALT) adapted by some cancer cells. Although the mechanism of how telomerase extends telomere length is well characterized, the mechanism of recombination-based ALT is still unclear. A telomeric long noncoding RNA termed telomeric repeat-containing RNA (TERRA) was identified in both mammalian cells and yeast. Using yeast S. cerevisiae as a model, our previous results show that TERRA was involved in telomere recombination, suggesting that TERRA formed RNA:DNA hybrid with telomeric DNA to stimulate telomere recombination in cells lacking telomerase. Here we focus on dissecting the mechanism of how TERRA stimulates telomere recombination. Analysis by genetic approaches showed that genes involved in nucleotide excision repair, RNA polymerase regulation and chromatin remodeling pathways play less significant roles in TERRA-mediated recombination. Surprisingly, we found deletion of RAD27, a 5' flap endonuclease required for Okazaki fragment processing and several repair pathways, induced early telomere recombination in a RNase H-dependent manner. Accumulation of short telomeric DNA fragments, a characteristic signature of ALT cells, was also observed in this deletion. Overexpression of EXO1 (encodes flap-endonuclease) and RNH1 (encodes RNase H) can rescue rad27 deletion defects. Further analysis showed that both total TERRA level and RNA:DNA hybrids accumulated in rad27 deletions. Preliminary biochemical analysis proved that Rad27 seemed to have the ability to cut R-loop substrates, but Rad27D179A endonuclease dead mutants failed to process R-loop substrates. These results reveal a new mechanism of how Rad27 processes and modulates long non-coding RNA TERRA to mediate telomere recombination. Since yeasts and human have very similar telomere structures, and rad27 mutants had been shown to occur in human tumors and inherited human diseases, our analyses highlight a possible pathway of telomere recombination and pathogenesis for the rad27 mutant diseases. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T02:51:05Z (GMT). No. of bitstreams: 1 ntu-106-R04442011-1.pdf: 4061888 bytes, checksum: bd4fca52e509a23933588c51ce89fdea (MD5) Previous issue date: 2017 | en |
dc.description.tableofcontents | 目錄
口試委員審定書.............................................................................i 致謝................................................................................................ii 中文摘要......................................................................................iii 英文摘要.......................................................................................iv 目錄...............................................................................................vi 附圖目錄......................................................................................vii 前言................................................................................................1 材料與方法....................................................................................9 結果..............................................................................................22 討論..............................................................................................31 參考文獻......................................................................................35 附圖..............................................................................................48 | |
dc.language.iso | zh-TW | |
dc.title | 探討酵母菌中長鏈非編碼核醣核酸TERRA影響端粒重組之機制 | zh_TW |
dc.title | Mechanistic analysis of long non-coding RNA TERRA affects telomere recombination in Saccharomyces cerevisiae | en |
dc.type | Thesis | |
dc.date.schoolyear | 105-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 鄧述諄(Shu-Chun Teng),冀宏源 | |
dc.subject.keyword | 端粒重組, | zh_TW |
dc.subject.keyword | TERRA,telomere recombination, | en |
dc.relation.page | 71 | |
dc.identifier.doi | 10.6342/NTU201703424 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2017-08-16 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 生物化學暨分子生物學研究所 | zh_TW |
顯示於系所單位: | 生物化學暨分子生物學科研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-106-1.pdf 目前未授權公開取用 | 3.97 MB | Adobe PDF |
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。