Изучение биохимических свойств белка Est3p, компонента теломеразного комплекса дрожжей Saccharomyces cerevisiae
Диссертация
Способность Est3p разворачивать ДНК/РНК гетеродуплексы может быть использована в процессе удлинения теломер теломеразным комплексом на стадии транслокации и влиять на процессивность этого комплекса. После синтеза теломеразой одного повтора образуется длинный комплементарный дуплекс теломерной ДНК с матричным участком теломеразной РНК, который должен быть хотя бы частично расплетен для того, чтобы… Читать ещё >
Содержание
- Список сокращений
- 1. Введение
- 2. Обзор литературы. Компоненты и регуляция длины теломер почкующихся дрожжей Saccharomyces cerevisiae
- 2. 1. Структура дрожжевых теломер
- 2. 1. 1. Теломерная ДНК дрожжей
- 2. 1. 2. Субтеломерные области дрожжевых хромосом
- 2. 1. 3. G-богатый одноцепочечный участок на 3'-конце
- 2. 2. Гены, влияющие на функции теломер
- 2. 3. Белки, взаимодействующие с G-богатым одноцепочечным участком теломер
- 2. 3. 1. Белок Cdcl
- 2. 3. 2. Теломеразный комплекс дрожжей Saccharomyces cerevisiae
- 2. 3. 2. 1. Коровый фермент. Tlcl и Est2p
- 2. 3. 2. 2. Estlp и Est3p — in vivo регуляторные компоненты теломеразного комплекса
- 2. 3. 3. Гетеродимер Ки
- 2. 3. 4. MRX комплекс
- 2. 4. Белки, взаимодействующие с двухцепочечным участком теломер
- 2. 4. 1. Белок Rapl и ассоциированные с ним факторы
- 2. 4. 2. Гетеродимер Ки как компонент двухцепочечной области теломер
- 2. 5. Регуляция структуры теломерного конца
- 2. 6. Регуляция длины теломер
- 2. 6. 1. Два состояния теломер
- 2. 6. 2. Теломеразное удлиннение G-богатого одноцепочечного участка прочно связано с полимеразным синтезом комплементарной цепи
- 2. 6. 3. Удлиннение теломер в течение клеточного цикла
- 2. 6. 4. Ассоциация компонентов теломеразного комплекса с теломерным хроматином
- 2. 6. 5. Контроль длины теломер с помощью рекомбинации
- 2. 6. 6. Контроль длины теломер с помощью Tell киназы
- 2. 1. Структура дрожжевых теломер
- 3. 1. Получение белка Est3p с аффинным эпитопом GST
- 3. 2. Взаимодействие Est3p с рибо- и дезоксирибоолигонуклеотидами
- 3. 3. Способность Est3p разворачивать дуплексы
- 3. 4. Влияние мутаций Е104А и 104RE на свойства Est3p
- 3. 5. Димеризация Est3p
- 3. 5. 1. Белок Est3p с различными аффинными эпитопами HaN- и С-концах
- 3. 5. 2. Образование гомодимера Est3p in vitro
- 3. 6. СТРазная и АТРазная активности белка Est3p
Список литературы
- Blackburn, Е.Н. (1991) Structure and Function of Telomeres. Nature 350: 569−572.
- Оловников, A.M. (1971) Принцип маргинотомии в матричном синтезе полинуклеотидов. Докл. АН СССР 201:1496−1499.
- Greider, C.W., and Blackburn, Е.Н. (1985) Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 43:405−413.
- Collins, K. (2000) Mammalian Telomeres and Telomerase. Curr. Op. Cell Biol. 12: 378−383.
- Harley, C.B., Futcher, A.B., and Greider, C.W. (1990) Telomeres shorten during ageing of human fibroblasts. Nature 345:458−460.
- Vaziri, H., Dragowska, W., Allsopp, R.C., Thomas, Т.Е., Harley, C.B., and Landsdorp, P.M. (1994) Evidence for a mitotic clock in human hematopoietic stem cells: loss of telomeric DNA with age. Proc. Natl. Acad. Sci. USA 91: 9857−9860.
- Hughes, T.R., Evans, S.R., Weilbaecher, R.G., and Lundbland, V. (2000) The Est3 protein is subunit of yeast telomerase. Curr. Biol. 10: 809−812.
- Lingner, J., Cech, T.R., Hughes, T.R., and Lundbland, V. (1997) Three Ever Shorter Telomere (EST) genes are dispensable for in vitro yeast telomerase activity. Proc. Natl. Acad. Sci. USA 94:11 190−11 195.
- Szostak, J.W., and Blackburn, E.H. (1982) Cloning yeast telomeres on linear plasmid vectors. Cell 29:245−255.
- Dunn, В., Szauter, P., Pardue, M.L., and Szostak, J.W. (1984) Transfer of yeast telomeres to linear plasmids by recombination. Cell 39:191−201.
- Horowitz, H., and Haber, J.E. (1985) Identification of autonomously replicating circular subtelomeric Y' elements in Saccharomyces cerevisiae. Mol. Cell Biol. 5: 2369−2380.
- Pluta, A.F., Dani, G.M., Spear, B.B., and Zakian, V.A. (1984) Elaboration of telomeres in yeast: recognition and modification of termini from Oxytricha macronuclear DNA. Proc. Natl. Acad. Sci. USA 81:1475−1479.
- Carson, M.J., and Hartwell, L. (1985) CDC 17: an essential gene that prevents telomere elongation in yeast. Cell 42:249−57.
- Lustig, A.J., and Petes, T.D. (1986) Identification of yeast mutants with altered telomere structure. Proc. Natl. Acad. Sei. USA 83:1398−1402.
- Meyne, J., Ratliff, R.L., and Moyzis, R.K. (1989) Conservation of the human telomere sequence (TTAGGG)n among vertebrates. Proc. Natl. Acad. Sei. USA 86:7049−7053.
- Higashiyama, T., Maki, S., and Yamada, T. (1995) Molecular organization of Chlorella vulgaris chromosome I: presence of telomeric repeats that are conserved in higher plants. Mol. Gen. Genet. 246:29−36.
- Richards, E.J., and Ausubel, F.M. (1988) Isolation of a higher eukaryotic telomere from Arabidopsis thaliana. Cell 53:127−136.
- Shakirov, E.V., and Shippen, D.E. (2004) Length regulation and dynamics of individual telomere tracts in wild-type Arabidopsis. Plant Cell 16:1959−1967.
- Fajkus, J., Kovarik, A., Kralovics, R., and Bezdek, M. (1995) Organization of telomeric and subtelomeric chromatin in the higher plant Nicotiana tabacum. Mol. Gen. Genet. 247:633−638.
- Blackburn, E.H., and Gall, J.G. (1978) A tandemly repeated sequence at the termini of the extrachromosomal ribosomal RNA genes in Tetrahymena. J. Mol. Biol. 120:33−53.
- Shampay, J., Szostak, J.W., and Blackburn, E.H. (1984) DNA sequences of telomeres maintained in yeast. Nature 310:154−157.
- Wang, S.S., and Zakian, V.A. (1990) Sequencing of Saccharomyces telomeres cloned using T4 DNA polymerase reveals two domains. Mol. Cell Biol. 10:4415−4419.
- Singer, M.S., and Gottschling, D.E. (1994) TLC1: template RNA component of Saccharomyces cerevisiae telomerase. Science 266:404−409.
- Prescott, J., and Blackburn, E.H. (1997) Functionally interacting telomerase RNAs in the yeast telomerase complex. Genes Dev. 11:2790−2800.
- Prescott, J., and Blackburn, E.H. (1997) Telomerase RNA mutations in Saccharomyces cerevisiae alter telomerase action and reveal nonprocessivity in vivo and in vitro. Genes Dev. 11:528−540.
- Forstemann, K., Hoss, M., and Lingner, J. (2000) Telomerase-dependent repeatdivergence at the 31 ends of yeast telomeres. Nucleic Acids Res. 28:2690−2694.
- Forstemann, K., and Lingner, J. (2001) Molecular basis for telomere repeat divergence in budding yeast. Mol. Cell Biol. 21: 7277−7286.
- Forstemann, K., and Lingner, J. (2005) Telomerase limits the extent of base pairing between template RNA and telomeric DNA. EMBO Rep. 6: 361−366.
- Cohn, M., McEachern, M.J., and Blackburn, E.H. (1998) Telomeric sequence diversity within the genus Saccharomyces. Curr. Genet. 33: 83−91.
- McEachern, M.J., and Hicks, J.B. (1993) Unusually large telomeric repeats in the yeast Candida albicans. Mol. Cell Biol. 13: 551−560.
- 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. USA 91: 3453−3457.
- Sugawara, N. 1998 DNA sequences at the telomeres of fission yeast S.pombe. Ph.D. thesis, Harvard University, Cambridge, Massachusetts.
- Mitton-Fry, R.M., Anderson, E.M., Theobald, D.L., Glustrom, L.W., and Wuttke, D.S. (2004) Structural basis for telomeric single-stranded DNA recognition by yeast Cdcl3. J. Mol. Biol. 338:241−255.
- Konig, P., and Rhodes, D. (1997) Recognition of telomeric DNA. Trends Biochem. Sci. 22:43−47.
- Teixeira, M.T., Arneric, M., Sperisen, P., and Lingner, J. (2004) Telomere length homeostasis is achieved via a switch between telomerase- extendible and -nonextendible states. Cell 117:323−335.
- Horowitz, H., Thorburn, P., and Haber, J.E. (1984) Rearrangements of highly polymorphic regions near telomeres of Saccharomyces cerevisiae. Mol. Cell Biol. 4: 2509−2517.
- 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.
- Shampay, J., and Blackburn, E.H. (1988) Generation of telomere-length heterogeneity in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 85: 534−538.
- Craven, R.J., and Petes, T.D. (1999) Dependence of the regulation of telomere length on the type of subtelomeric repeat in the yeast Saccharomyces cerevisiae. Genetics 152:1531−1541.
- Chan, C.S., and Tye, B.K. (1983) A family of Saccharomyces cerevisiae repetitive autonomously replicating sequences that have very similar genomic environments. J.1. Mol. Biol. 168:505−523.
- Chan, C.S., and Tye, B.K. (1983) Organization of DNA sequences and replication origins at yeast telomeres. Cell 33: 563−573.
- Louis, E.J. (1995) The chromosome ends of Saccharomyces cerevisiae. Yeast 11: 1553−1573.
- Murray, A.W., and Szostak, J.W. (1983) Construction of artificial chromosomes in yeast. Nature 305:189−193.
- Pryde, F.E., and Louis, E.J. (1999) Limitations of silencing at native yeast telomeres. EMBOJ. 18:2538−2550.
- Pryde, F.E., and Louis, E.J. (1997) Saccharomyces cerevisiae telomeres. A review. Biochemistry 62:1232−1241.
- Lundblad, V., and Blackburn, E.H. (1993) An alternative pathway for yeast telomere maintenance rescues estl- senescence. Cell 73:347−360.
- Makarov, V.L., Hirose, Y., and Langmore, J.P. (1997) Long G tails at both ends of human chromosomes suggest a C strand degradation mechanism for telomere shortening. Cell 88: 657−666.
- Wellinger, R.J., Wolf, A. J., and Zakian, V.A. (1993) Saccharomyces telomeres acquire single-strand TG1−3 tails late in S phase. Cell 72:51−60.
- Larrivee, M., LeBel, C., and Wellinger, RJ. (2004) The generation of proper constitutive G-tails on yeast telomeres is dependent on the MRX complex. Genes Dev. 18:1391−1396.
- Griffith, J.D., Comeau, L., Rosenfield, S., Stansel, R.M., Bianchi, A., Moss, H., and de Lange, T. (1999) Mammalian telomeres end in a large duplex loop. Cell 97:503−514.
- Tomaska, L., Willcox, S., Slezakova, J., Nosek, J., and Griffith, J.D. (2004) Tazl binding to a fission yeast model telomere: formation of telomeric loops and higher order structures. J. Biol. Chem. 279: 50 764−50 772.
- Shore, D., and Nasmyth, K. (1987) Purification and cloning of a DNA binding protein from yeast that binds to both silencer and activator elements. Cell 51: 721−732.
- Lustig, A.J., Kurtz, S., and Shore, D. (1990) Involvement of the silencer and UAS binding protein RAP1 in regulation of telomere length. Science 250:549−553.
- Nugent, C.I., Hughes, T.R., Lue, N.F., and Lundblad, V. (1996) Cdcl3p: a singlestrand telomeric DNA-binding protein with a dual role in yeast telomere maintenance. Science 274:249−252.
- Runge, K.W., and Zakian, V.A. (1996) TEL2, an essential gene required for telomere length regulation and telomere position effect in Saccharomyces cerevisiae. Mol. Cell. Biol 16: 3094−3105.
- Grandin, N., Reed, S.I., and Charbonneau, M. (1997) Stnl, a new Saccharomyces cerevisiae protein, is implicated in telomere size regulation in association with Cdcl3. Genes Dev. 11:512−527.
- Grossi, S., Puglisi, A., Dmitriev, P.V., Lopes, M., and Shore, D. (2004) Pol 12, the B subunit of DNA polymerase alpha, functions in both telomere capping and length regulation. Genes Dev. 18: 992−1006.
- Garvik, B., Carson, M., and Hartwell, L. (1995) Single-stranded DNA arising at telomeres in cdcl3 mutants may constitute a specific signal for the RAD9 checkpoint. Mol. Cell. Biol. 15:6128−6138.
- Booth, C., Griffith, E., Brady, G., and Lydall, D. (2001) Quantitative amplification of single-stranded DNA (QAOS) demonstrates that cdcl3-l mutants generate ssDNA in a telomere to centromere direction. Nucleic Acids Res. 29:4414−4422.
- Hackett, J.A., Feldser, D.M., and Greider, C.W. (2001) Telomere dysfunction increases mutation rate and genomic instability. Cell 106:275−286.
- Craven, R.J., Greenwell, P.W., Dominska, M., and Petes, T.D. (2002) Regulation of genome stability by TEL1 and MEC1, yeast homologs of the mammalian ATM and ATR genes. Genetics 161:493−507.
- Chan, S.W., and Blackburn, E.H. (2003) Telomerase and ATM/Tellp protect telomeres from nonhomologous end joining. Mol. Cell 11:1379−1387.
- Hackett, J.A., and Greider, C.W. (2003) End resection initiates genomic instability in the absence of telomerase. Mol. Cell Biol. 23: 8450−8461.
- Mieczkowski, P.A., Mieczkowska, J.O., Dominska, M., and Petes, T.D. (2003) Genetic regulation of telomere-telomere fusions in the yeast Saccharomyces cerevisae.
- Proc. Natl. Acad. Sci. USA 100:10 854−10 859.
- Hartwell, L.H., Mortimer, R.K., Culotti, J., and Culotti, M. (1973) Genetic Control of the Cell Division Cycle in Yeast: V. Genetic Analysis of cdc Mutants. Genetics 74: 267−286.
- Weinert, T.A., and Hartwell, L.H. (1993) Cell cycle arrest of cdc mutants and specificity of the RAD9 checkpoint. Genetics 134:63−80.
- Lydall, D., and Weinert, T. (1995) Yeast checkpoint genes in DNA damage processing: implications for repair and arrest. Science 270:1488−1491.
- Grandin, N., Damon, C., and Charbonneau, M. (2001) Tenl functions in telomere end protection and length regulation in association with Stnl and Cdcl3. EMBO J. 20: 1173−1183.
- Pennock, E., Buckley, K., and Lundblad, V. (2001) Cdcl3 delivers separate complexes to the telomere for end protection and replication. Cell 104: 387−396.
- Evans, S.K., and Lundblad, V. (2000) Positive and negative regulation of telomerase access to the telomere. J. Cell Sci. 19:3357−3364.
- 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.
- Evans, S.K., and Lundblad, V. (1999) Estl and Cdcl3 as comediators of telomerase access. Science 286:117−120.
- Bianchi, A., Negrini, S., and Shore, D. (2004) Delivery of yeast telomerase to a DNA break depends on the recruitment functions of Cdcl3 and Estl. Mol. Cell 16:139−146.
- Chandra, A., Hughes, T.R., Nugent, C.I., and Lundblad, V. (2001) Cdcl3 both positively and negatively regulates telomere replication. Genes Dev. 15:404−414.
- Qi, H., and Zakian, V.A. (2000) The Saccharomyces Telomere-Binding Protein Cdcl3p Interacts With Both the Catalytic Subunit of DNA Polymerase a and the Telomerase-Associated Estl Protein Genes Dev. 14:1777−1788.
- Mitton-Fry, R.M., Anderson, E.M., Hughes, T.R., Lundblad, V., and Wuttke, D.S. (2002) Conserved structure for single-stranded telomeric DNA recognition. Science 296:145−147.
- Murzin, A.G. (1993) OB(oligonucleotide/oligosaccharide binding)-fold: common structural and functional solution for non-homologous sequences. EMBO J. 12: 861 867.
- Horvath, M.P., Schweiker, V.L., Bevilacqua, J.M., Ruggles, J.A., and Schultz, S.C.1998) Crystal structure of the Oxytricha nova telomere end binding protein complexed with single strand DNA. Cell 95:963−974.
- Lei, M., Podell, E.R., Baumann, P., and Cech, T.R. (2003) DNA self-recognition in the structure of Potl bound to telomeric single-stranded DNA. Nature 426:198−203.
- Theobald, D.L., Cervantes, R.B., Lundblad, V., and Wuttke, D.S. (2003) Homology among telomeric end-protection proteins. Structure 11:1049−1050.
- Theobald, D.L., and Wuttke, D.S. (2004) Prediction of multiple tandem OB-fold domains in telomere end-binding proteins Potl and Cdcl3. Structure 12:1877−1879.
- Taggart, A.K., Teng, S.C., and Zakian, V.A. (2002) Estlp as a cell cycle-regulated activator of telomere-bound telomerase. Science 297:1023−1026.
- Schramke, V., Luciano, P., Brevet, V., Guillot, S., Corda, Y., Longhese, M.P., Gilson, E., and Geli, V. (2004) RPA regulates telomerase action by providing Estlp access to chromosome ends. Nat. Genet. 36:46−54.
- Fisher, T.S., Taggart, A.K., and Zakian, V.A. (2004) Cell cycle-dependent regulation of yeast telomerase by Ku. Nat. Struct. Mol. Biol. 11:1198−1205.
- Baumann, P., and Cech, T.R. (2001) Potl, the putative telomere end-binding protein in fission yeast and humans. Science 292:1171−1175.
- Greider, C.W., and Blackburn, E.H. (1989) A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis. Nature 337:331−337.
- Lingner, J., and Cech, T.R. (1996) Purification of telomerase from Euplotes aediculatus: requirement of a primer 3' overhang. Proc. Natl. Acad. Sci. USA 93: 10 712−10 717.
- Witkin, K.L., and Collins, K. (2004) Holoenzyme proteins required for the physiological assembly and activity of telomerase. Genes Dev. 18:1107−1118.
- Lundblad, V., and Szostak, J.W. (1989) A mutant with a defect in telomere elongation leads to senescence in yeast. Cell 57: 633−643.
- Singer, M.S., Kahana, A., Wolf, A.J., Meisinger, L.L., Peterson, S.E., Goggin, C., Mahowald, M., and Gottschling, D.E. (1998) Identification of high-copy disruptors of telomeric silencing in Saccharomyces cerevisiae. Genetics 150: 613−632.
- Diede, S.J., and Gottschling, D.E. (1999) Telomerase-mediated telomere addition in vivo requires DNA primase and DNA polymerases alpha and delta. Cell 99: 723−733.
- Friedman, K.L., Heit, J.J., Long, D.M., and Cech, T.R. (2003) N-terminal domain of yeast telomerase reverse transcriptase: recruitment of Est3p to the telomerase complex. Mol. Biol. Cell 14:1−13.
- Marcand, S., Brevet, V., and Gilson, E. (1999) Progressive cis-inhibition of telomerase upon telomere elongation. EMBOJ. 18: 3509−3519.
- Singh, S.M., Steinberg-Neifach, O., Mian, I.S., and Lue, N.F. (2002) Analysis of telomerase in Candida albicans: potential role in telomere end protection. Eukaryot Cell 1: 967−977.
- Steinberg-Neifach, O., and Lue, N.F. (2006) Modulation of telomere terminal structure by telomerase components in Candida albicans. Nucleic. Acids Res. 34:2710−2722.
- Bhattacharyya, A., and Blackburn, E.H. (1997) A functional telomerase RNA swap in vivo reveals the importance of nontemplate RNA domains. Proc. Natl. Acad. Sei. USA 94:2823−2827.
- Roy, J., Fulton, T.B., and Blackburn, E.H. (1998) Specific telomerase RNA residues distant from the template are essential for telomerase function. Genes Dev. 12: 3286−3300.
- McCormick-Graham, M., and Romero, D.P. (1995) Ciliate telomerase RNA structural features. Nucleic Acids Res. 23:1091−1097.
- McEachern, M.J., and Blackburn, E.H. (1995) Runaway telomere elongation caused by telomerase RNA gene mutations. Nature 376:403−409.
- Blasco, M.A., Funk, W., Villeponteau, B., and Greider, C.W. (1995) Functional characterization and developmental regulation of mouse telomerase RNA. Science 269: 1267−1270.
- Tsao, D.A., Wu, C.W., and Lin, Y.S. (1998) Molecular cloning of bovine telomerase RNA. Gene 221: 51−58.
- Ares, M.Jr. (1986) U2 RNA from yeast is unexpectedly large and contains homology to vertebrate U4, U5, and U6 small nuclear RNAs. Cell 47:49−59.
- Chen, J.L., and Greider, C.W.(2004) An emerging consensus for telomerase RNA structure. Proc. Natl. Acad. Sei. USA 101:14 683−14 684.
- Lustig, A. J. (2004) Telomerase RNA: a flexible RNA scaffold for telomerase biosynthesis. Curr. Biol. 14: 565−567.
- Ly, H., Blackburn, E.H., and Parslow, T.G. (2003) Comprehensive structure-function analysis of the core domain of human telomerase RNA. Mol. Cell Biol. 23:6849−6856.
- Zappulla, D.C., and Cech, T.R. (2004) Yeast telomerase RNA: a flexible scaffold for protein subunits. Proc. Natl. Acad. Sci. USA 101: 10 024−10 029.
- Dandjinou, A.T., Levesque, N., Larose, S., Lucier, J.F., Abou Elela, S., and Wellinger, R. J. (2004) A phylogenetically based secondary structure for the yeast telomerase RNA. Curr. Biol. 14:1148−1158.
- Livengood, A.J., Zaug, A.J., and Cech, T.R. (2002) Essential regions of Saccharomyces cerevisiae telomerase RNA: separate elements for Estlp and Est2p interaction. Mol. Cell Biol. 22: 2366−231A.
- Seto, A.G., Livengood, A.J., Tzfati, Y., Blackburn, E.H., and Cech, T.R. (2002) A bulged stem tethers Estlp to telomerase RNA in budding yeast. Genes Dev. 16: 2800−2812.
- Seto, A.G., Zaug, A.J., Sobel, S.G., Wolin, S.L., and Cech, T.R. (1999) Saccharomyces cerevisiae telomerase is an Sm small nuclear ribonucleoprotein particle. Nature 401:177−180.
- Peterson, S.E., Stellwagen, A.E., Diede, S.J., Singer, M.S., Haimberger, Z.W., Johnson, C.O., Tzoneva, M., and Gottschling, D.E. (2001) The function of a stem-loop in telomerase RNA is linked to the DNA repair protein Ku. Nat. Genet. 27: 64−67.
- Stellwagen, A.E., Haimberger, Z.W., Veatch, J.R., and Gottschling, D.E. (2003) Ku interacts with telomerase RNA to promote telomere addition at native and broken chromosome ends. Genes Dev. 17:2384−2395.
- Will, C.L., and Luhrmann, R. (2001) Spliceosomal UsnRNP biogenesis, structure and function. Curr. Opin. Cell Biol. 13:290−301.
- Henning, K.A., Moskowitz, N., Ashlock, M.A., and Liu, P.P. (1998) Humanizing the yeast telomerase template. Proc. Natl. Acad. Sci. USA 95: 5667−5671.
- Tzfati, Y., Fulton, T.B., Roy, J., and Blackburn, E.H. (2000) Template boundary in a yeast telomerase specified by RNA structure. Science 288: 863−867.
- Tzfati, Y., Knight, Z., Roy, J., and Blackburn, E.H. (2003) A novel pseudoknot element is essential for the action of a yeast telomerase. Genes Dev. 17:1779−1788.
- Chen, J.L., Blasco, M.A., and Greider, C.W. (2000) Secondary structure ofvertebrate telomerase RNA. Cell 100: 503−514.
- Chapon, C., Cech, T.R. and Zaug, A.J. (1997) Polyadenylation of telomerase RNA in budding yeast. RNA 3:1337−1351.
- Prowse, K.R., Avilion, A. A., and Greider, C.W. (1993) Identification of a nonprocessive telomerase activity from mouse cells. Proc. Natl. Acad. Sci. USA 90: 1493−1497.
- 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.
- Kelleher, C., Teixeira, M.T., Forstemann, K., and Lingner, J. (2002) Telomerase: biochemical considerations for enzyme and substrate. Trends Biochem. Sci. 27: 572−579.
- Friedman, K.L., and Cech, T.R. (1999) Essential functions of amino-terminal domains in the yeast telomerase catalytic subunit revealed by selection for viable mutants. Genes Dev. 13:2863−2874.
- Peng, Y., Mian, I.S. and Lue, N.F. (2001) Analysis of telomerase processivity: mechanistic similarity to HIV-1 reverse transcriptase and role in telomere maintenance. Mol. Cell 7:1201−1211.
- Lue, N.F., Lin, Y.C. and Mian, I.S. (2003) A conserved telomerase motif within the catalytic domain of telomerase reverse transcriptase is specifically required for repeat addition processivity. Mol. Cell Biol. 23: 8440−8449.
- Teixeira, M.T., Forstemann, K., Gasser, S.M., and Lingner, J. (2002) Intracellular trafficking of yeast telomerase components. EMBO Rep. 3:652−659.
- Cohn, M., and Blackburn, E.H. (1995) Telomerase in yeast. Science 269: 396 400.
- Virta-Pearlman, V., Morris, D.K., and Lundblad, V. (1996) Estl has the properties of a single-stranded telomere end-binding protein. Genes Dev. 10:30 943 104.
- Zhou, J., Hidaka, K., and Futcher, B. (2000) The Estl subunit of yeast telomerase binds the Tlcl telomerase RNA. Mol. Cell Biol. 20:1947−1955.
- Evans, S.K., and Lundblad, V. (2002) The Estl subunit of Saccharomyces cerevisiae telomerase makes multiple contributions to telomere length maintenance. Genetics 162:1101−1115.
- Clissold, P.M., and Ponting, C.P. (2000) PIN domains in nonsense-mediatedmRNA decay and RNAi. Curr. Biol. 10: 888−890.
- Beernink, H.T., Miller, K., Deshpande, A., Bucher, P., and Cooper, J.P. (2003) Telomere maintenance in fission yeast requires an Estl ortholog. Curr. Biol. 13: 575 580.
- Reichenbach, P., Hoss, M., Azzalin, C.M., Nabholz, M., Bucher, P., and Lingner, J. (2003) A human homolog of yeast Estl associates with telomerase and uncaps chromosome ends when overexpressed. Curr. Biol. 13: 568−574.
- Snow, B.E., Erdmann, N., Cruickshank, J., Goldman, H., Gill, R.M., Robinson, M.O., and Harrington, L. (2003) Functional conservation of the telomerase protein Estlp in humans. Curr. Biol. 13:698−704.
- D’Andrea, L.D., and Regan, L. (2003) TPR proteins: the versatile helix. Trends Biochem. Sci. 28: 655−662.
- Singh, S, M" and Lue, N.F. (2003) Ever shorter telomere 1 (ESTl)-dependent reverse transcription by Candida telomerase in vitro: evidence in support of an activating function. Proc. Natl. Acad. Sci. USA 100: 5718−5723.
- Morris, D.K., and Lundblad, V. (1997) Programmed translational frameshifting in a gene required for yeast telomere replication. Curr. Biol. 7: 969−976.
- Taliaferro, D., and Farabaugh, P.J. (2007) An mRNA sequence derived from the yeast EST3 gene stimulates programmed +1 translational frameshifting. RNA 13: 606−613.
- Clare, J.J., Belcourt, M., and Farabugh, P.J. (1998) Efficient translation frameshifting occurs within a conserved sequence of overlap between the two genes of yeast Tyl transposon Proc. Natl. Acad. Sci. USA 85: 6816−6820.
- Belcourt, M., and Farabugh, P.J. (1990) Ribosomal frameshifting in the yeast retrotransposon Ty: tRNAs induce slippage on 7 nucleotide minimal site Cell 62:339 352.
- Voytas, D.F., and Boeke, J.D. (1993) Yeast retrotransposon and tRNAs Trends Genet. 9:421−427.
- Downs, J.A., and Jackson, S.P. (2004) A means to a DNA end: the many roles of Ku. Nat. Rev. Mol. Cell Biol. 5:367−378.
- Tuteja, R., and Tuteja, N. (2000) Ku autoantigen: a multifunctional DNA-binding protein. Crit. Rev. Biochem. Mol. Biol. 35:1−33.
- Boulton, S.J., and Jackson, S.P. (1998) Components of the Ku-dependent nonhomologous end-joining pathway are involved in telomeric length maintenance andtelomeric silencing. EMBO J. 17: 1819−1828.
- Laroche, T., Martin, S.G., Gotta, M., Gorham, H.C., Pryde, F.E., Louis, E.J., and Gasser, S.M. (1998) Mutation of yeast Ku genes disrupts the subnuclear organization of telomeres. Curr. Biol. 8:653−656.
- Hediger, F., Neumann, F.R., Van Houwe, G., Dubrana, K., and Gasser, S.M. (2002) Live imaging of telomeres: yKu and Sir proteins define redundant telomere-anchoring pathways in yeast. Curr. Biol. 12:2076−2089.
- Boulton, S.J., and Jackson, S.P. (1996) Identification of a Saccharomyces cerevisiae Ku80 homologue: roles in DNA double strand break rejoining and in telomeric maintenance. Nucleic Acids Res. 24:4639−4648.
- Porter, S.E., Greenwell, P.W., Ritchie, K.B., and Petes, T.D. (1996) The DNA-binding protein Hdflp (a putative Ku homologue) is required for maintaining normal telomere length in Saccharomyces cerevisiae. Nucleic Acids Res. 24: 582−585.
- Gravel, S., Larrivee, M., Labrecque, P., and Wellinger, R.J. (1998) Yeast Ku as a regulator of chromosomal DNA end structure. Science 280: 741−744.
- Polotnianka, R.M., Li, J., and Lustig, A.J. (1998) The yeast Ku heterodimer is essential for protection of the telomere against nucleolytic and recombinational activities. Curr. Biol. 8: 831−834.
- Walker, J.R., Corpina, R.A., and Goldberg, J. (2001) Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair. Nature 412:607−614.
- Kramer, K.M., and Haber, J.E. (1993) New telomeres in yeast are initiated with a highly selected subset of TGI-3 repeats. Genes Dev. 7:2345−2356.
- Kolodner, R.D., Putnam, C.D., and Myung, K. (2002) Maintenance of genome stability in Saccharomyces cerevisiae. Science 297:552−557.
- Chen, C., and Kolodner, R.D. (1999) Gross chromosomal rearrangements in Saccharomyces cerevisiae replication and recombination defective mutants. Nat. Genet. 23: 81−85.
- Myung, K., Datta, A., and Kolodner, R.D. (2001) Suppression of spontaneous chromosomal rearrangements by S phase checkpoint functions in Saccharomyces cerevisiae. Cell 104:397−408.
- Bertuch, A.A., and Lundblad, V. (2004) EXOl contributes to telomere maintenance in both telomerase-proficient and telomerase-deficient Saccharomyces cerevisiae. Genetics 166:1651−1659.
- Maringele, L., Lydall, D. (2002) EXO1 -dependent single-stranded DNA at telomeres activates subsets of DNA damage and spindle checkpoint pathways in budding yeast yku70Delta mutants. Genes Dev. 16:1919−1933.
- Moreau, S., Morgan, E.A., and Symington, L.S. (2001) Overlapping functions of the Saccharomyces cerevisiae Mrel 1, Exol and Rad27 nucleases in DNA metabolism. Genetics 159:1423−1433.
- Bertuch, A. A., and Lundblad, V. (2003) The Ku heterodimer performs separable activities at double-strand breaks and chromosome termini. Mol. Cell Biol. 23: 8202−8215.
- Cosgrove, A.J., Nieduszynski, C.A., and Donaldson, A.D. (2002) Ku complex controls the replication time of DNA in telomere regions. Genes Dev. 16:2485−2490.
- Dionne, I., and Wellinger, R.J. (1998) Processing of telomeric DNA ends requires the passage of a replication fork. Nucleic Acids Res. 26: 5365−5371.
- Stracker, T.H., Theunissen, J.W., Morales, M" and Petrini, J.H. (2004) The Mrel 1 complex and the metabolism of chromosome breaks: the importance of communicating and holding things together. DNA Repair. (Amst.) 3: 845−854.
- Lichten, M. (2005) Rad50 connects by hook or by crook. Nat. Struct. Mol. Biol. 12:392−393.
- Kironmai, K.M., and Muniyappa, K. (1997) Alteration of telomeric sequences and senescence caused by mutations in RAD50 of Saccharomyces cerevisiae. Genes Cells 2:443−455.
- Nugent, C.I., Bosco, G., Ross, L.O., Evans, S.K., Salinger, A.P., Moore, J.K., Haber, J.E., and Lundblad, V. (1998) Telomere maintenance is dependent on activities required for end repair of double-strand breaks. Curr. Biol. 8: 657−660.
- Ritchie, K.B., and Petes, T.D. (2000) The Mrel Ip/Rad50p/Xrs2p complex and the Tellp function in a single pathway for telomere maintenance in yeast. Genetics 155:475−479.
- Diede, S.J., and Gottschling, D.E. (2001) Exonuclease activity is required for sequence addition and Cdcl3p loading at a de novo telomere. Curr. Biol. 11:13 361 340.
- Tsukamoto, Y., Taggart, A.K., and Zakian, V.A. (2001) The role of the Mrel 1-Rad50-Xrs2 complex in telomerase- mediated lengthening of Saccharomyces cerevisiae telomeres. Curr. Biol. 11:1328−1335.
- Lewis, L.K., Karthikeyan, G., Westmoreland, J. W" and Resnick, M.A. (2002)
- Differential suppression of DNA repair deficiencies of Yeast rad50, mrel 1 and xrs2 mutants by EXOl and TLC1 (the RNA component of telomerase). Genetics 160:4962.
- Li, B., and Lustig, A.J. (1996) A novel mechanism for telomere size control in Saccharomyces cerevisiae. Genes Dev. 10:1310−1326.
- Bucholc, M., Park, Y., and Lustig, A.J. (2001) Intrachromatid excision of telomeric DNA as a mechanism for telomere size control in Saccharomyces cerevisiae. Mol. Cell Biol. 21:6559−6573.
- Takata, H., Tanaka, Y., and Matsuura, A. (2005) Late S phase-specific recruitment of Mrel 1 complex triggers hierarchical assembly of telomere replication proteins in Saccharomyces cerevisiae. Mol. Cell 17:573−583.
- Konig, P., Giraldo, R., Chapman, L., and Rhodes, D. (1996) The crystal structure of the DNA-binding domain of yeast RAP1 in complex with telomeric DNA. Cell 85:125−136.
- Conrad, M.N., Wright, J.H., Wolf, A.J., and Zakian, V.A. (1990) RAP 1 protein interacts with yeast telomeres in vivo: overproduction alters telomere structure and decreases chromosome stability. Cell 63:739−750.
- Kyrion, G., Boakye, K.A., and Lustig, A.J. (1992) C-terminal truncation of RAP1 results in the deregulation of telomere size, stability, and function in Saccharomyces cerevisiae. Mol. Cell Biol. 12:5159−5173.
- Marcand, S., Gilson, E., and Shore, D. (1997) A protein-counting mechanism for telomere length regulation in yeast. Science 275: 986−990.
- Levy, D.L., and Blackburn, E.H. (2004) Counting of Rifl p and Rif2p on Saccharomyces cerevisiae telomeres regulates telomere length. Mol. Cell Biol. 24: 10 857−10 867.
- Tsukamoto, Y., Kato, J., and Ikeda, H. (1997) Silencing factors participate in DNA repair and recombination in Saccharomyces cerevisiae. Nature 388: 900−903.
- Mishra, K., and Shore, D. (1999) Yeast Ku protein plays a direct role in telomeric silencing and counteracts inhibition by rif proteins. Curr. Biol. 9:1123−1126.
- Roy, R., Meier, B., McAinsh, A.D., Feldmann, H.M., and Jackson, S.P. (2004)
- Separation-of-function mutants of yeast Ku80 reveal a Yku80p-Sir4p interaction involved in telomeric silencing. J. Biol. Chem. 279: 86−94.
- Wellinger, R.J., Ethier, K., Labrecque, P., and Zakian, V.A. (1996) Evidence for a new step in telomere maintenance. Cell 85:423−433.
- Jia, X., Weinert, T., and Lydall, D. (2004) Mecl and Rad53 inhibit formation of single-stranded DNA at telomeres of Saccharomyces cerevisiae cdcl3-l mutants. Genetics 166:753−764.
- Zubko, M.K., Guillard, S., and Lydall, D. (2004) Exo 1 and Rad24 differentially regulate generation of ssDNA at telomeres of Saccharomyces cerevisiae cdcl3-l mutants. Genetics 168:103−115.
- Fan, X., and Price, C.M. (1997) Coordinate regulation of G- and C strand length during new telomere synthesis. Mol. Biol. Cell 8:2145−2155.
- Adams, A.K., and Holm, C. (1996) Specific DNA replication mutations affect telomere length in Saccharomyces cerevisiae. Mol. Cell Biol. 16:4614−4620.
- Adams Martin, A., Dionne, I., Wellinger, R.J., and Holm, C. (2000) The function of DNA polymerase alpha at telomeric G tails is important for telomere homeostasis. Mol. Cell Biol. 20:786−796.
- Marcand, S., Brevet, V., Mann, C., and Gilson, E. (2000) Cell cycle restriction of telomere elongation. Curr. Biol. 10:487−490.
- Bianchi, A., and Shore, D. (2007) Early Replication of Short Telomeres in Budding Yeast. Cell 128:1051−1062.
- Smith, C.D., Smith, D.L., DeRisi, J.L., and Blackburn, E.H. (2003) Telomeric protein distributions and remodeling through the cell cycle in Saccharomyces cerevisiae. Mol. Biol. Cell 14: 556−570.
- Williams, B., Bhattacharyya, M.K., and Lustig, A.J. (2005) Mre 11 p nuclease activity is dispensable for telomeric rapid deletion. DNA Repair. (Amst.) 4:994−1005.
- Garber, P.M., Vidanes, G.M., and Toczyski, D.P. (2005) Damage in transition. Trends Biochem. Sci. 30: 63−66.
- Ritchie, K.B., Mallory, J.C., and Petes, T.D. (1999) Interactions of TLC1 (Which Encodes the RNA Subunit of Telomerase), TEL1, and MEC1 in Regulating Telomere Length in the Yeast Saccharomyces cerevisiae. Mol. Cell Biol. 19:60 656 075.
- Takata, H., Kanoh, Y., Gunge, N., Shirahige, K., and Matsuura, A. (2004) Reciprocal association of the budding yeast ATM-related proteins Tell and Mecl withtelomeres in vivo. Mol. Cell 14: 515−522.
- Yang, C.P., Chen, Y.B., Meng, F.L., and Zhou, J.Q. (2006) Saccharomyces cerevisiae Est3p dimerizes in vitro and dimerization contributes to efficient telomere replication in vivo. Nucleic Acids Res. 34: 407−416.
- Funaba, M., and Mathews, L.S. (2000) Recombinant expression and purification of smad proteins. Protein Expr. Pur if. 20: 507−513.
- Lejeune, D., Delsaux, N., Charloteaux, B., Thomas, A., and Brasseur, R. (2005) Protein-nucleic acid recognition: statistical analysis of atomic interactions and influence of DNA structure. Proteins 61: 258−271.
- Moriarty, T.J., Huard, S., Dupuis, S., and Autexier, C. (2002) Functional multimerization of human telomerase requires an RNA interaction domain in the N terminus of the catalytic subunit. Mol. Cell Biol. 22: 1253−1265.
- Beattie, T.L., Zhou, W., Robinson, M.O., and Harrington, L. (2001) Functional multimerization of the human telomerase reverse transcriptase. Mol. Cell Biol. 21: 6151−6160.
- Wenz, C., Enenkel, B., Amacker, M., Kelleher, C., Damm, K., and Lingner, J. (2001) Human telomerase contains two cooperating telomerase RNA molecules. EMBOJ. 20: 3526−3534.
- Wang, L., Dean, S.R., and Shippen, D.E. (2002) Oligomerization of the telomerase reverse transcriptase ftom Euplotes crassus. Nucleic Acids Res. 30:40 324 039.
- Hsiao, K. (1993) Exonuclease III induced ligase-free directional subcloning of PCR products. Nucleic Acids Res. 21:5528−5529.
- Lobau, S., Weber, J., Wilke-Mounts, S., and Senior, A.E. (1997) Fl-ATPase, roles of three catalytic site residues. J. Biol. Chem. 272: 3648−3656.
- Senior, A.E., Nadanaciva, S., and Weber, J. (2000) Rate acceleration of ATP hydrolysis by F (l)F (o)-ATP synthase. J. Exp. Biol. 203: 35−40.
- Tombline, G., Bartholomew, L.A., Tyndall, G.A., Gimi, K., Urbatsch, I.L., and Senior, A.E. (2004) Properties of P-glycoprotein with mutations in the «catalytic carboxylate» glutamate residues. J. Biol. Chem. 279: 46 518−46 526.
- Zanetti, L., Ristoratore, F., Bertoni, A., and Cariello, L. (2004) Characterization of sea urchin transglutaminase, a protein regulated by guanine/adenine nucleotides. J. Biol. Chem. 279:49 289−49 297.
- Najafi, S.M., Harris, D.A., and Yudkin, M.D. (1996) The SpoIIAA protein of Bacillus subtilis has GTP-binding properties. J. Bacteriol. 178: 6632−6634.
- Bergara, F., Ibarra, C., Iwamasa, J., Patarroyo, J.C., Aguilera, R., and Marquez-Magana, L.M. (2003) CodY is a nutritional repressor of flagellar gene expression in Bacillus subtilis. J. Bacteriol. 185: 3118−3126.
- Levdikov, V.M., Blagova, E., Joseph, P., Sonenshein, A.L., and Wilkinson, A.J. (2006) The structure of CodY, a GTP- and isoleucine-responsive regulator of stationary phase and virulence in gram-positive bacteria. J. Biol. Chem. 281:1 136 611 373.
- Bourne, H.R., Sanders, D.A., and McCormick, F. (1991) The GTPase superfamily: conserved structure and molecular mechanism. Nature 349:117−127.
- Niu, H., Xia, J., and Lue, N.F. (2000) Characterization of the interaction between the nuclease and reversetranscriptase activity of the yeast telomerase complex. Mol. Cell Biol. 20: 6806−6815.
- Moriarty, T.J., Marie-Egyptienne, D.T., and Autexier, C. (2004) Functional organization of repeat addition processivity and DNA synthesis determinants in the human telomerase multimer. Mol. Cell Biol. 24: 3720−3733.
- Collins, K., and Gandhi, L. (1998) The reverse transcriptase component of the Tetrahymena telomerase ribonucleoprotein complex. Proc. Natl. Acad. Sci. USA 95: 8485−8490.
- Bryan, T.M., Goodrich, K.J., and Cech, T.R. (2000) A mutant of Tetrahymena telomerase reverse transcriptase with increased processivity. J. Biol. Chem. 275: 24 199−24 207.
- Sambrook, J., and Russell, D.W. (2001) Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory Press.
- Laemmli, U.K. (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227: 680−685.