人的类RecD解旋酶Pif1通过抑制端粒酶活性调控端粒延伸
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摘要
端粒是真核生物线状染色体的末端结构,由端粒DNA和其结合蛋白组成。它在维持基因组的稳定、防止染色体DNA末端融合和降解中起着重要的作用,并与癌症、衰老密切相关。端粒DNA重复序列的延伸是由特化的反转录酶即端粒酶完成的。端粒酶的核心组分是由具有催化活性的蛋白质亚基(hTERT)和RNA亚基(hTR)组成,hTR为合成端粒DNA重复序列提供模板。
以前的研究发现芽殖酵母Pif1解旋酶通过抑制端粒酶途径来抑制端粒DNA的加长。端粒DNA复制的基本机制从酵母到人都高度保守,而类Pif1基因在多种生物中都广泛存在。因而,本研究的主要目的是鉴定人Pif1蛋白,是否也参与了端粒DNA的复制和维持。本工作首先克隆了人Pif1的cDNA。一级结构及生化分析表明,人Pif1蛋白是大肠杆菌RecD潜在的同源蛋白;具有依赖于ATP的5'至3'的DNA解旋酶活性。在端粒酶阳性的HT1080细胞中过表达野生型hPif1蛋白可导致细胞端粒DNA缩短,抑制hPif1过表达可使端粒DNA长度恢复。人Pif1对端粒DNA长度的影响需要其ATPase/解旋酶活性,因为丧失ATPase/解旋酶活性的突变体过表达不影响端粒DNA的长度。在端粒酶阴性的GM487细胞中过表达hPif1不影响端粒变化,提示hPif1蛋白对端粒DNA的效应是通过端粒酶通路介导的。体外生化实验还显示,重组Pif1蛋白可通过降低端粒酶的进行性从而直接抑制端粒酶的活性,而且,hPif1解旋酶能够解开DNA/RNA杂合双螺旋。染色质免疫沉淀还证实hPif1结合在端粒DNA上。基于这些实验结果,我们推测hPif1通过把端粒酶RNA从端粒DNA上解离下来而抑制端粒酶介导端粒DNA的加长。类RecD解旋酶在生物进化过程中已获得新功能。
Telomeres are nucleoprotein structures that are positioned at eukaryotic linearchromosomal ends. The primary role of telomeres is to insulate the chromosomal endsfrom both fusion with other ends and from nucleolytic digestion. The stablemaintenance of telomeres contributes to genome stability, and correlates with cancerand aging. The telomerase is a specialized reverse transcriptase that extends the 3' endof the G-rich strand of telomeres.
The Saccharomyces Pif1 helicase inhibits telomere lengthening through thetelomerase pathway. Pif1-like genes are found in diverse organisms. Because thefundamental mechanism of telomere replication is highly conserved from yeast tomammals, we want to know whether hPif1 exists, and what the role of hPif1 plays inhuman. Here, we identified a human helicase, hPif1, that inhibits telomerase activity.The primary sequence and biochemical analysis suggest that hPif1 is a potentialhomologue of Escherichia coli RecD, an ATP-dependent 5' to 3' DNA helicase.Ectopic expression of wild-type, but not the ATPase/helicase deficient hPif1, causestelomere shortening in HT1080 cells. hPif1 inhibits human telomerase activityprobably due to reducing the repeat addition processivity of telomerase in vitro. hPif1could unwind DNA/RNA duplex and preferentially binds telomeric DNA in vitro andin vivo. We propose that the inhibitory mechanism of hPif1 on telomerase involvesunwinding of the DNA/RNA duplex formed by telomerase RNA and telomeric DNA.RecD homologues in eukaryotes may have evolved gaining additional functions.
以前的研究发现芽殖酵母Pif1解旋酶通过抑制端粒酶途径来抑制端粒DNA的加长。端粒DNA复制的基本机制从酵母到人都高度保守,而类Pif1基因在多种生物中都广泛存在。因而,本研究的主要目的是鉴定人Pif1蛋白,是否也参与了端粒DNA的复制和维持。本工作首先克隆了人Pif1的cDNA。一级结构及生化分析表明,人Pif1蛋白是大肠杆菌RecD潜在的同源蛋白;具有依赖于ATP的5'至3'的DNA解旋酶活性。在端粒酶阳性的HT1080细胞中过表达野生型hPif1蛋白可导致细胞端粒DNA缩短,抑制hPif1过表达可使端粒DNA长度恢复。人Pif1对端粒DNA长度的影响需要其ATPase/解旋酶活性,因为丧失ATPase/解旋酶活性的突变体过表达不影响端粒DNA的长度。在端粒酶阴性的GM487细胞中过表达hPif1不影响端粒变化,提示hPif1蛋白对端粒DNA的效应是通过端粒酶通路介导的。体外生化实验还显示,重组Pif1蛋白可通过降低端粒酶的进行性从而直接抑制端粒酶的活性,而且,hPif1解旋酶能够解开DNA/RNA杂合双螺旋。染色质免疫沉淀还证实hPif1结合在端粒DNA上。基于这些实验结果,我们推测hPif1通过把端粒酶RNA从端粒DNA上解离下来而抑制端粒酶介导端粒DNA的加长。类RecD解旋酶在生物进化过程中已获得新功能。
Telomeres are nucleoprotein structures that are positioned at eukaryotic linearchromosomal ends. The primary role of telomeres is to insulate the chromosomal endsfrom both fusion with other ends and from nucleolytic digestion. The stablemaintenance of telomeres contributes to genome stability, and correlates with cancerand aging. The telomerase is a specialized reverse transcriptase that extends the 3' endof the G-rich strand of telomeres.
The Saccharomyces Pif1 helicase inhibits telomere lengthening through thetelomerase pathway. Pif1-like genes are found in diverse organisms. Because thefundamental mechanism of telomere replication is highly conserved from yeast tomammals, we want to know whether hPif1 exists, and what the role of hPif1 plays inhuman. Here, we identified a human helicase, hPif1, that inhibits telomerase activity.The primary sequence and biochemical analysis suggest that hPif1 is a potentialhomologue of Escherichia coli RecD, an ATP-dependent 5' to 3' DNA helicase.Ectopic expression of wild-type, but not the ATPase/helicase deficient hPif1, causestelomere shortening in HT1080 cells. hPif1 inhibits human telomerase activityprobably due to reducing the repeat addition processivity of telomerase in vitro. hPif1could unwind DNA/RNA duplex and preferentially binds telomeric DNA in vitro andin vivo. We propose that the inhibitory mechanism of hPif1 on telomerase involvesunwinding of the DNA/RNA duplex formed by telomerase RNA and telomeric DNA.RecD homologues in eukaryotes may have evolved gaining additional functions.
引文
[1] Akalin, A., Elmore, L. W., Forsythe, H. L., Amaker, B. A., McCollum, E. D., Nelson, P. S., Ware, J. L., and Holt, S. E. (2001). A novel mechanism for chaperone-mediated telomerase regulation during prostate cancer progression. Cancer Res 61, 4791-4796.
[2] Akimov, S. S., Ramezani, A., Hawley, T. S., and Hawley, R. G. (2005). Bypass of senescence, immortalization, and transformation of human hematopoietic progenitor cells. Stem Cells 23, 1423-1433.
[3] Akiyama, Y., Maesawa, C., Wada, K., Fujisawa, K., Itabashi, T., Noda, Y., Honda, T., Sato, N., Ishida, K., Takagane, A., et al. (2004). Human PinX1, a potent telomerase inhibitor, is not involved in human gastrointestinal tract carcinoma. Oncol Rep 11, 871-874.
[4] Allshire, R. C., Gosden, J. R., Cross, S. H., Cranston, G., Rout, D., Sugawara, N., Szostak, J. W., Fantes, P. A., and Hastie, N. D. (1988). Telomeric repeat from T. thermophila cross hybridizes with human telomeres. Nature 332, 656-659.
[5] Amundsen, S. K., Taylor, A. F., and Smith, G. R. (2002). A domain of RecC required for assembly of the regulatory RecD subunit into the Escherichia coli RecBCD holoenzyme. Genetics 161, 483-492.
[6] Anderson, E. M., Halsey, W. A., and Wuttke, D. S. (2002). Delineation of the high-affinity single-stranded telomeric DNA-binding domain of Saccharomyces cerevisiae Cdc13. Nucleic Acids Res 30, 4305-4313.
[7] Armbruster, B. N., Linardic, C. M., Veldman, T., Bansal, N. P., Downie, D. L., and Counter, C. M. (2004). Rescue of an hTERT mutant defective in telomere elongation by fusion with hPot1. Mol Cell Biol 24, 3552-3561.
[8] Backer, J., and Foury, F. (1985). Repair properties in yeast mitochondrial DNA mutators. Curr Genet 10, 7-13.
[9] Banik, S. S., and Counter, C. M. (2004). Characterization of interactions between PinX1 and human telomerase subunits hTERT and hTR. J Biol Chem.
[10] Baroin, A., Prat, A., and Caron, F. (1987). Telomeric site position heterogeneity in macronuclear DNA of Paramecium primaurelia. Nucleic Acids Res 15, 1717-1728.
[11] Baumann, P., Podell, E., and Cech, T. R. (2002). Human Pot1 (protection of telomeres) protein: cytolocalization, gene structure, and alternative splicing. Mol Cell Biol 22, 8079-8087.
[12] Bessler, J. B., Torredagger, J. Z., and Zakian, V. A. (2001). The Pif1p subfamily of helicases: region-specific DNA helicases? Trends Cell Biol 11, 60-65.
[13] Bhattacharyya, S., and Lahue, R. S. (2005). Srs2 helicase of Saccharomyces cerevisiae selectively unwinds triplet repeat DNA. J Biol Chem 280, 33311-33317.
[14] Bilaud, T., Brun, C., Ancelin, K., Koering, C. E., Laroche, T., and Gilson, E. (1997). Telomeric localization of TRF2, a novel human telobox protein. Nat Genet 17, 236-239.
[15] Blackburn, E. H. (1990a). Telomeres and their synthesis. Harvey Lect 86, 1-18.
[16] Blackburn, E. H. (1990b). Telomeres: structure and synthesis. J Biol Chem 265, 5919-5921.
[17] 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.
[18] Blasco, M. A. (2003). Mammalian telomeres and telomerase: why they matter for cancer and aging. Eur J Cell Biol 82, 441-446.
[19] Boltze, C., Lehnert, H., Schneider-Stock, R., Peters, B., Hoang Vu, C., and Roessner, A. (2004). Withdrawal. HSP90 is a key for telomerase activation and malignant transition in pheochromocytoma. Endocrine 23, 229.
[20] Boule, J. B., Vega, L. R., and Zakian, V. A. (2005). The yeast Pif1p helicase removes telomerase from telomeric DNA. Nature.
[21] Boveri, T. (1887). ber Differenzierung der Zellkerne wthrend der Fiirchung des
[22] Eies von Ascaris megalocephala. Anat Ariz 2, 688-693.
[23] Broccoli, D., Smogorzewska, A., Chong, L., and de Lange, T. (1997). Human telomeres contain two distinct Myb-related proteins, TRF1 and TRF2. Nat Genet 17, 231-235.
[24] 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.
[25] 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.
[26] Buczek, P., Orr, R. S., Pyper, S. R., Shum, M., Kimmel, E., Ota, I., Gerum, S. E., and Horvath, M. P. (2005). Binding linkage in a telomere DNA-protein complex at the ends of Oxytricha nova chromosomes. J Mol Biol 350, 938-952.
[27] Budarf, M. L., and Blackburn, E. H. (1986). Chromatin structure of the telomeric region and 3'-nontranscribed spacer of Tetrahymena ribosomal RNA genes. J Biol Chem 261, 363-369.
[28] Budd, M. E., Choe, W., and Campbell, J. L. (2000). The nuclease activity of the yeast DNA2 protein, which is related to the RecB-like nucleases, is essential in vivo. J Biol Chem 275, 16518-16529.
[29] Budd, M. E., Reis, C. C., Smith, S., Myung, K., and Campbell, J. L. (2006). Evidence suggesting that Pif1 helicase functions in DNA replication with the Dna2 helicase/nuclease and DNA polymerase delta. Mol Cell Biol 26, 2490-2500.
[30] Burma, S., and Chen, D. J. (2004). Role of DNA-PK in the cellular response to DNA double-strand breaks. DNA Repair (Amst) 3, 909-918.
[31] Chai, W., Ford, L. P., Lenertz, L., Wright, W. E., and Shay, J. W. (2002). Human Ku70/80 associates physically with telomerase through interaction with hTERT. J Biol Chem 277, 47242-47247.
[32] Chang, W., Dynek, J. N., and Smith, S. (2003). TRF1 is degraded by ubiquitin-mediated proteolysis after release from telomeres. Genes Dev 17, 1328-1333.
[33] Chong, L., van Steensel, B., Broccoli, D., Erdjument-Bromage, H., Hanish, J., Tempst, P., and de Lange, T. (1995). A human telomeric protein. Science 270, 1663-1667.
[34] Classen, S., Ruggles, J. A., and Schultz, S. C. (2001). Crystal structure of the N-terminal domain of Oxytricha nova telomere end-binding protein alpha subunit both uncomplexed and complexed with telomeric ssDNA. J Mol Biol 314, 1113-1125.
[35] Cohen, H., and Sinclair, D. A. (2001). Recombination-mediated lengthening of terminal telomeric repeats requires the Sgs1 DNA helicase. Proc Natl Acad Sci U S A 98, 3174-3179.
[36] Colgin, L. M., Baran, K., Baumann, P., Cech, T. R., and Reddel, R. R. (2003). Human POT1 facilitates telomere elongation by telomerase. Curr Biol 13, 942-946.
[37] Colgin, L. M., Wilkinson, C., Englezou, A., Kilian, A., Robinson, M. O., and Reddel, R. R. (2000). The hTERTalpha splice variant is a dominant negative inhibitor of telomerase activity. Neoplasia 2, 426-432.
[38] Cooper, J. P., Nimmo, E. R., Allshire, R. C., and Cech, T. R. (1997). Regulation of telomere length and function by a Myb-domain protein in fission yeast. Nature 385, 744-747.
[39] Counter, C. M., Avilion, A. A., LeFeuvre, C. E., Stewart, N. G., Greider, C. W., Harley, C. B., and Bacchetti, S. (1992). Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity. Embo J 11, 1921-1929.
[40] Counter, C. M., Hahn, W. C., Wei, W., Caddle, S. D., Beijersbergen, R. L., Lansdorp, P. M., Sedivy, J. M., and Weinberg, R. A. (1998). Dissociation among in vitro telomerase activity, telomere maintenance, and cellular immortalization. Proc Natl Acad Sci U S A 95, 14723-14728.
[41] Cowell, J. K., and Miller, O. J. (1983). Occurrence and evolution of homogeneously staining regions may be due to breakage-fusion-bridge cycles following telomere loss. Chromosoma 88, 216-221.
[42] Crabbe, L., Verdun, R. E., Haggblom, C. I., and Karlseder, J. (2004). Defective telomere lagging strand synthesis in cells lacking WRN helicase activity. Science 306, 1951-1953.
[43] d'Adda di Fagagna, F., Teo, S. H., and Jackson, S. P. (2004). Functional links between telomeres and proteins of the DNA-damage response. Genes Dev 18, 1781-1799.
[44] Dawson, D., and Herrick, G. (1984). Telomeric properties of C4A4-homologous sequences in micronuclear DNA of Oxytricha fallax. Cell 36, 171-177.
[45] de Lange, T. (1992). Human telomeres are attached to the nuclear matrix. Embo J 11, 717-724.
[46] de Lange, T., Shiue, L., Myers, R. M., Cox, D. R., Naylor, S. L., Killery, A. M., and Varmus, H. E. (1990). Structure and variability of human chromosome ends. Mol Cell Biol 10, 518-527.
[47] Debabov, V. G. (1979). [DNA unwinding proteins]. Usp Sovrem Biol 87, 170-184.
[48] Deloukas, P., Schuler, G. D., Gyapay, G., Beasley, E. M., Soderlund, C., Rodriguez-Tome, P., Hui, L., Matise, T. C., McKusick, K. B., Beckmann, J. S., et al. (1998). A physical map of 30,000 human genes. Science 282, 744-746.
[49] Dermic, D. (2006). Functions of multiple exonucleases are essential for cell viability, DNA repair and homologous recombination in recD mutants of Escherichia coli. Genetics.
[50] Dermic, D., Halupecki, E., Zahradka, D., and Petranovic, M. (2005). RecBCD enzyme overproduction impairs DNA repair and homologous recombination in Escherichia coli. Res Microbiol 156, 304-311.
[51] Dettlaff-Pokora, A., and Schlichtholz, B. (2003). [Alternative lengthening of telomeres]. Postepy Biochem 49, 147-156.
[52] Dhar, S., Squire, J. A., Hande, M. P., Wellinger, R. J., and Pandita, T. K. (2000). Inactivation of 14-3-3sigma influences telomere behavior and ionizing radiation-induced chromosomal instability. Mol Cell Biol 20, 7764-7772.
[53] Dillingham, M. S., Spies, M., and Kowalczykowski, S. C. (2003). RecBCD enzyme is a bipolar DNA helicase. Nature 423, 893-897.
[54] Dillingham, M. S., Webb, M. R., and Kowalczykowski, S. C. (2005). Bipolar DNA translocation contributes to highly processive DNA unwinding by RecBCD enzyme. J Biol Chem 280, 37069-37077.
[55] Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., Pereira-Smith, O., and et al. (1995). A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci U S A 92, 9363-9367.
[56] Du, X., Shen, J., Kugan, N., Furth, E. E., Lombard, D. B., Cheung, C., Pak, S., Luo, G., Pignolo, R. J., DePinho, R. A., et al. (2004). Telomere shortening exposes functions for the mouse Werner and Bloom syndrome genes. Mol Cell Biol 24, 8437-8446.
[57] Eitner, G., Solonin, A. S., and Tanyashin, V. I. (1981). Cloning of a recA-like gene of Proteus mirabilis. Gene 14, 301-308.
[58] Ellis, N. A., Groden, J., Ye, T. Z., Straughen, J., Lennon, D. J., Ciocci, S., Proytcheva, M., and German, J. (1995). The Bloom's syndrome gene product is homologous to RecQ helicases. Cell 83, 655-666.
[59] Emery, H. S., and Weiner, A. M. (1981). An irregular satellite sequence is found at the termini of the linear extrachromosomal rDNA in Dictyostelium discoideum. Cell 26, 411-419.
[60] Fang, G., and Cech, T. R. (1993). The beta subunit of Oxytricha telomere-binding protein promotes G-quartet formation by telomeric DNA. Cell 74, 875-885.
[61] Fisher, T. S., and Zakian, V. A. (2005). Ku: A multifunctional protein involved in telomere maintenance. DNA Repair (Amst).
[62] Ford, L. P., Wright, W. E., and Shay, J. W. (2002). A model for heterogeneous nuclear ribonucleoproteins in telomere and telomerase regulation. Oncogene 21, 580-583.
[63] Forney, J., Henderson, E. R., and Blackburn, E. H. (1987). Identification of the telomeric sequence of the acellular slime molds Didymium iridis and Physarum polycephalum. Nucleic Acids Res 15, 9143-9152.
[64] Forney, J. D., and Blackburn, E. H. (1988). Developmentally controlled telomere addition in wild-type and mutant paramecia. Mol Cell Biol 8, 251-258.
[65] Forsythe, H. L., Elmore, L. W., Jensen, K. O., Landon, M. R., and Holt, S. E. (2002). Retroviral-mediated expression of telomerase in normal human cells provides a selective growth advantage. Int J Oncol 20, 1137-1143.
[66] Foury, F., and Kolodynski, J. (1983). pif mutation blocks recombination between mitochondrial rho+ and rho-genomes having tandemly arrayed repeat units in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 80, 5345-5349.
[67] Foury, F., and Lahaye, A. (1987). Cloning and sequencing of the PIF gene involved in repair and recombination of yeast mitochondrial DNA. Embo J 6, 1441-1449.
[68] Frank-Vaillant, M., and Marcand, S. (2001). NHEJ regulation by mating type is exercised through a novel protein, Lif2p, essential to the ligase IV pathway. Genes Dev 15, 3005-3012.
[69] George, J. W., Ghate, S., Matson, S. W., and Besterman, J. M. (1992). Inhibition of DNA helicase II unwinding and ATPase activities by DNA-interacting ligands. Kinetics and specificity. J Biol Chem 267, 10683-10689.
[70] Gonzalez, I. L., Petersen, R., and Sylvester, J. E. (1989). Independent insertion of Alu elements in the human ribosomal spacer and their concerted evolution. Mol Biol Evol 6, 413-423.
[71] Gorbalenya, A. E., Koonin, E. V., Donchenko, A. P., and Blinov, V. M. (1989). Two related superfamilies of putative helicases involved in replication, recombination, repair and expression of DNA and RNA genomes. Nucleic Acids Res 17, 4713-4730.
[72] Gray, J. T., Celander, D. W., Price, C. M., and Cech, T. R. (1991). Cloning and expression of genes for the Oxytricha telomere-binding protein: specific subunit interactions in the telomeric complex. Cell 67, 807-814.
[73] Greider, C. W. (1999). Telomeres do D-loop-T-loop. Cell 97, 419-422.
[74] Greider, C. W., and Blackburn, E. H. (1985). Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 43, 405-413.
[75] Gu, J., Xia, X., Yan, P., Liu, H., Podust, V. N., Reynolds, A. B., and Fanning, E. (2004). Cell cycle-dependent regulation of a human DNA helicase that localizes in DNA damage foci. Mol Biol Cell 15, 3320-3332.
[76] H. J. Muller, S., 84 . (1927). Science 46, 84.
[77] Harley, C. B., and Kim, N. W. (1996). Telomerase and cancer. Important Adv Oncol, 57-67.
[78] Hayakawa, S., Kaneko, H., Fukao, T., Kasahara, K., Matsumoto, T., Furuichi, Y., and Kondo, N. (2000). Characterization of the nuclear localization signal in the DNA helicase responsible for Bloom syndrome. Int J Mol Med 5, 477-484.
[79] Heacock, M., Spangler, E., Riha, K., Puizina, J., and Shippen, D. E. (2004). Molecular analysis of telomere fusions in Arabidopsis: multiple pathways for chromosome end-joining. Embo J 23, 2304-2313.
[80] Higashibata, H., Kikuchi, H., Kawarabayasi, Y., and Matsui, I. (2003). Helicase and nuclease activities of hyperthermophile Pyrococcus horikoshii Dna2 inhibited by substrates with RNA segments at 5'-end. J Biol Chem 278, 15983-15990.
[81] 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.
[82] Hotta, Y., and Stern, H. (1978). DNA unwinding protein from meiotic cells of Lilium. Biochemistry 17, 1872-1880.
[83] Hsu, H. L., Gilley, D., Blackburn, E. H., and Chen, D. J. (1999). Ku is associated with the telomere in mammals. Proc Natl Acad Sci U S A 96, 12454-12458.
[84] Huang, P., Pryde, F. E., Lester, D., Maddison, R. L., Borts, R. H., Hickson, I. D., and Louis, E. J. (2001). SGS1 is required for telomere elongation in the absence of telomerase. Curr Biol 11, 125-129.
[85] Ivessa, A. S., Zhou, J. Q., Schulz, V. P., Monson, E. K., and Zakian, V. A. (2002). Saccharomyces Rrm3p, a 5' to 3' DNA helicase that promotes replication fork progression through telomeric and subtelomeric DNA. Genes Dev 16, 1383-1396.
[86] Ivessa, A. S., Zhou, J. Q., and Zakian, V. A. (2000). The Saccharomyces Pif1p DNA helicase and the highly related Rrm3p have opposite effects on replication fork progression in ribosomal DNA. Cell 100, 479-489.
[87] Johnson, F. B., Marciniak, R. A., McVey, M., Stewart, S. A., Hahn, W. C., and Guarente, L. (2001). The Saccharomyces cerevisiae WRN homolog Sgs1p participates in telomere maintenance in cells lacking telomerase. Embo J 20, 905-913.
[88] Kaminker, P. G., Kim, S. H., Taylor, R. D., Zebarjadian, Y., Funk, W. D., Morin, G. B., Yaswen, P., and Campisi, J. (2001). TANK2, a new TRF1-associated poly(ADP-ribose) polymerase, causes rapid induction of cell death upon overexpression. J Biol Chem 276, 35891-35899.
[89] Kartalou, M., and Essigmann, J. M. (2001). Recognition of cisplatin adducts by cellular proteins. Mutat Res 478, 1-21.
[90] Kim, J. H., Park, S. M., Kang, M. R., Oh, S. Y., Lee, T. H., Muller, M. T., and Chung, I. K. (2005). Ubiquitin ligase MKRN1 modulates telomere length homeostasis through a proteolysis of hTERT. Genes Dev 19, 776-781.
[91] 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.
[92] Kim, S. H., Kaminker, P., and Campisi, J. (1999). TIN2, a new regulator of telomere length in human cells. Nat Genet 23, 405-412.
[93] Kimura, A., Ohmichi, M., Kawagoe, J., Kyo, S., Mabuchi, S., Takahashi, T., Ohshima, C., Arimoto-Ishida, E., Nishio, Y., Inoue, M., et al. (2004). Induction of hTERT expression and phosphorylation by estrogen via Akt cascade in human ovarian cancer cell lines. Oncogene 23, 4505-4515.
[94] Kishi, S., Wulf, G., Nakamura, M., and Lu, K. P. (2001). Telomeric protein Pin2/TRF1 induces mitotic entry and apoptosis in cells with short telomeres and is down-regulated in human breast tumors. Oncogene 20, 1497-1508.
[95] Kitao, S., Shimamoto, A., Goto, M., Miller, R. W., Smithson, W. A., Lindor, N. M., and Furuichi, Y. (1999). Mutations in RECQL4 cause a subset of cases of Rothmund-Thomson syndrome. Nat Genet 22, 82-84.
[96] Klapper, W., Krams, M., Qian, W., Janssen, D., and Parwaresch, R. (2003). Telomerase activity in B-cell non-Hodgkin lymphomas is regulated by hTERT transcription and correlated with telomere-binding protein expression but uncoupled from proliferation. Br J Cancer 89, 713-719.
[97] Klobutcher, L. A., Swanton, M. T., Donini, P., and Prescott, D. M. (1981). All gene-sized DNA molecules in four species of hypotrichs have the same terminal sequence and an unusual 3' terminus. Proc Natl Acad Sci U S A 78, 3015-3019.
[98] Kramer, K. M., and Haber, J. E. (1993). New telomeres in yeast are initiated with a highly selected subset of TG1-3 repeats. Genes Dev 7, 2345-2356.
[99] Lahaye, A., Leterme, S., and Foury, F. (1993a). PIF1 DNA helicase from Saccharomyces cerevisiae. Biochemical characterization of the enzyme. J Biol Chem 268, 26155-26161.
[100] Lahaye, A., Leterme, S., and Foury, F. (1993b). PIF1 DNA helicase from Saccharomyces cerevisiae. Biochemical characterization of the enzyme. J Biol Chem 268, 26155-26161.
[101] Lahaye, A., Stahl, H., Thines-Sempoux, D., and Foury, F. (1991). PIF1: a DNA helicase in yeast mitochondria. Embo J 10, 997-1007.
[102] Lahaye, A., Stahl, H., Thines, S. D., and Foury, F (1991). PIF1: a DNA helicase in yeast mitochondria. Embo J 10, 997-1007.
[103] Lee, J. W., Harrigan, J., Opresko, P. L., and Bohr, V. A. (2005). Pathways and functions of the Werner syndrome protein. Mech Ageing Dev 126, 79-86.
[104] Lei, M., Podell, E. R., and Cech, T. R. (2004). Structure of human POT1 bound to telomeric single-stranded DNA provides a model for chromosome end-protection. Nat Struct Mol Biol 11, 1223-1229.
[105] Lei, M., Zaug, A. J., Podell, E. R., and Cech, T. R. (2005). Switching human telomerase on and off with hPOT1 protein in vitro. J Biol Chem.
[106] Li, B., and de Lange, T. (2003). Rap1 affects the length and heterogeneity of human telomeres. Mol Biol Cell 14, 5060-5068.
[107] Li, B., Oestreich, S., and de Lange, T. (2000). Identification of human Rap1: implications for telomere evolution. Cell 101, 471-483.
[108] Lin, Y. C., Shih, J. W., Hsu, C. L., and Lin, J. J. (2001). Binding and partial denaturing of G-quartet DNA by Cdc13p of Saccharomyces cerevisiae. J Biol Chem 276, 47671-47674.
[109] Lingner, J., and Cech, T. R. (1998). Telomerase and chromosome end maintenance. Curr Opin Genet Dev 8, 226-232.
[110] Liu, D., O'Connor, M. S., Qin, J., and Songyang, Z. (2004). Telosome --A mammalian telomere associated complex formed by multiple telomeric proteins. J Biol Chem.
[111] Loayza, D., and De Lange, T. (2003). POT1 as a terminal transducer of TRF1 telomere length control. Nature 423, 1013-1018.
[112] Lohman, T. M., and Bjornson, K. P. (1996). Mechanisms of helicase-catalyzed DNA unwinding. Annu Rev Biochem 65, 169-214.
[113] Lundblad, V., and Blackburn, E. H. (1993). An alternative pathway for yeast telomere maintenance rescues est1-senescence. Cell 73, 347-360.
[114] Lustig, A. J. (2001). Cdc13 subcomplexes regulate multiple telomere functions. Nat Struct Biol 8, 297-299.
[115] Machwe, A., Xiao, L., and Orren, D. K. (2006). Length-dependent degradation of single-stranded 3' ends by the Werner syndrome protein (WRN): implications for spatial orientation and coordinated 3' to 5' movement of its ATPase/helicase and exonuclease domains. BMC Mol Biol 7, 6.
[116] Marcand, S., Gilson, E., and Shore, D. (1997). A protein-counting mechanism for telomere length regulation in yeast. Science 275, 986-990.
[117] Marchler-Bauer, A., and Bryant, S. H. (2004). CD-Search: protein domain annotations on the fly. Nucleic Acids Res 32, W327-331.
[118] Matson, S. W. (1991). DNA helicases of Escherichia coli. Prog Nucleic Acid Res Mol Biol 40, 289-326.
[119] Matson, S. W., and Kaiser-Rogers, K. A. (1990). DNA helicases. Annu Rev Biochem 59, 289-329.
[120] Matsumoto, T., Fukui, K., Niwa, O., Sugawara, N., Szostak, J. W., and Yanagida, M. (1987). Identification of healed terminal DNA fragments in linear minichromosomes of Schizosaccharomyces pombe. Mol Cell Biol 7, 4424-4430.
[121] Matsutani, N., Yokozaki, H., Tahara, E., Tahara, H., Kuniyasu, H., Kitadai, Y., Haruma, K., Chayama, K., and Yasui, W. (2001). Expression of MRE11 complex (MRE11, RAD50, NBS1) and hRap1 and its relation with telomere regulation, telomerase activity in human gastric carcinomas. Pathobiology 69, 219-224.
[122] Mattern, K. A., Swiggers, S. J., Nigg, A. L., Lowenberg, B., Houtsmuller, A. B., and Zijlmans, J. M. (2004). Dynamics of protein binding to telomeres in living cells: implications for telomere structure and function. Mol Cell Biol 24, 5587-5594.
[123] McClintock, B. (1941). The stability of broken ends of chromosomes in Zea mays. Genetics 26, 234?282.
[124] McEachern, M. J., Krauskopf, A., and Blackburn, E. H. (2000). Telomeres and their control. Annu Rev Genet 34, 331-358.
[125] Meyerson, M. (1998). Telomerase enzyme activation and human cell immortalization. Toxicol Lett 102-103, 41-45.
[126] Meyne, J., Ratliff, R. L., and Moyzis, R. K. (1989). Conservation of the human telomere sequence (TTAGGG)n among vertebrates. Proc Natl Acad Sci U S A 86, 7049-7053.
[127] 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 Cdc13. J Mol Biol 338, 241-255.
[128] Mohanty, B. K., Bairwa, N. K., and Bastia, D. (2006). The Tof1p-Csm3p protein complex counteracts the Rrm3p helicase to control replication termination of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 103, 897-902.
[129] Morin, G. B. (1989). The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesizes TTAGGG repeats. Cell 59, 521-529.
[130] 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.
[131] Muller, B., Boehmer, P. E., Emmerson, P. T., and West, S. C. (1991). Action of RecBCD enzyme on Holliday structures made by RecA. J Biol Chem 266, 19028-19033.
[132] Muller, H. (1938). The remaking of chromosomes. Collecting Net , 8.
[133] Nakamura, M., Zhou, X. Z., Kishi, S., Kosugi, I., Tsutsui, Y., and Lu, K. P. (2001). A specific interaction between the telomeric protein Pin2/TRF1 and the mitotic spindle. Curr Biol 11, 1512-1516.
[134] O'Connor, M. S., Safari, A., Liu, D., Qin, J., and Songyang, Z. (2004). The human Rap1 protein complex and modulation of telomere length. J Biol Chem 279, 28585-28591.
[135] O'Rourke, T. W., Doudican, N. A., Zhang, H., Eaton, J. S., Doetsch, P. W., and Shadel, G. S. (2005). Differential involvement of the related DNA helicases Pif1p and Rrm3p in mtDNA point mutagenesis and stability. Gene 354, 86-92.
[136] Ogawa, T., Shinohara, A., Nabetani, A., Ikeya, T., Yu, X., Egelman, E. H., and Ogawa, H. (1993). RecA-like recombination proteins in eukaryotes: functions and structures of RAD51 genes. Cold Spring Harb Symp Quant Biol 58, 567-576.
[137] Oka, Y., Shiota, S., Nakai, S., Nishida, Y., and Okubo, S. (1980). Inverted terminal repeat sequence in the macronuclear DNA of Stylonychia pustulata. Gene 10, 301-306.
[138] Opresko, P. L., Otterlei, M., Graakjaer, J., Bruheim, P., Dawut, L., Kolvraa, S., May, A., Seidman, M. M., and Bohr, V. A. (2004). The Werner Syndrome Helicase and Exonuclease Cooperate to Resolve Telomeric D Loops in a Manner Regulated by TRF1 and TRF2. Mol Cell 14, 763-774.
[139] Opresko, P. L., von Kobbe, C., Laine, J. P., Harrigan, J., Hickson, I. D., and Bohr, V. A. (2002). Telomere-binding protein TRF2 binds to and stimulates the Werner and Bloom syndrome helicases. J Biol Chem 277, 41110-41119.
[140] Paeschke, K., Simonsson, T., Postberg, J., Rhodes, D., and Lipps, H. J. (2005). Telomere end-binding proteins control the formation of G-quadruplex DNA structures in vivo. Nat Struct Mol Biol 12, 847-854.
[141] Palmbos, P. L., Daley, J. M., and Wilson, T. E. (2005). Mutations of the Yku80 C terminus and Xrs2 FHA domain specifically block yeast nonhomologous end joining. Mol Cell Biol 25, 10782-10790.
[142] Patel, S. S., and Picha, K. M. (2000). Structure and function of hexameric helicases. Annu Rev Biochem 69, 651-697.
[143] Peersen, O. B., Ruggles, J. A., and Schultz, S. C. (2002). Dimeric structure of the Oxytricha nova telomere end-binding protein alpha-subunit bound to ssDNA. Nat Struct Biol 9, 182-187.
[144] Phillips, R. J., Hickleton, D. C., Boehmer, P. E., and Emmerson, P. T. (1997). The RecB protein of Escherichia coli translocates along single-stranded DNA in the 3' to 5' direction: a proposed ratchet mechanism. Mol Gen Genet 254, 319-329.
[145] Pluta, A. F., Kaine, B. P., and Spear, B. B. (1982). The terminal organization of macronuclear DNA in Oxytricha fallax. Nucleic Acids Res 10, 8145-8154.
[146] Richards, E. J., and Ausubel, F. M. (1988). Isolation of a higher eukaryotic telomere from Arabidopsis thaliana. Cell 53, 127-136.
[147] Rigden, D. J. (2005). An inactivated nuclease-like domain in RecC with novel function: implications for evolution. BMC Struct Biol 5, 9.
[148] Ryu, G. H., Tanaka, H., Kim, D. H., Kim, J. H., Bae, S. H., Kwon, Y. N., Rhee, J. S., MacNeill, S. A., and Seo, Y. S. (2004). Genetic and biochemical analyses of Pfh1 DNA helicase function in fission yeast. Nucleic Acids Res 32, 4205-4216.
[149] Salaj-Smic, E., Dermic, D., Brcic-Kostic, K., Cajo, G. C., and Trgovcevic, E. (2000). In vivo studies of the Escherichia coli RecB polypeptide lacking its nuclease center. Res Microbiol 151, 769-776.
[150] Sanchez-Alonso, P., and Guzman, P. (1998). Organization of chromosome ends in Ustilago maydis. RecQ-like helicase motifs at telomeric regions. Genetics 148, 1043-1054.
[151] Sandell, L. L., and Zakian, V. A. (1993). Loss of a yeast telomere: arrest, recovery, and chromosome loss. Cell 75, 729-739.
[152] Schulz, V. P., and Zakian, V. A. (1994). The saccharomyces PIF1 DNA helicase inhibits telomere elongation and de novo telomere formation. Cell 76, 145-155.
[153] Seimiya, H., Sawada, H., Muramatsu, Y., Shimizu, M., Ohko, K., Yamane, K., and Tsuruo, T. (2000). Involvement of 14-3-3 proteins in nuclear localization of telomerase. Embo J 19, 2652-2661.
[154] Shampay, J., Szostak, J. W., and Blackburn, E. H. (1984). DNA sequences of telomeres maintained in yeast. Nature 310, 154-157.
[155] Shen, M., Haggblom, C., Vogt, M., Hunter, T., and Lu, K. P. (1997). Characterization and cell cycle regulation of the related human telomeric proteins Pin2 and TRF1 suggest a role in mitosis. Proc Natl Acad Sci U S A 94, 13618-13623.
[156] Shinohara, A., Ogawa, H., and Ogawa, T. (1992). Rad51 protein involved in repair and recombination in S. cerevisiae is a RecA-like protein. Cell 69, 457-470.
[157] Simonsson, T. (2001). The human TINF2 gene organisation and chromosomal localization. Biochimie 83, 433-435.
[158] Singleton, M. R., Dillingham, M. S., Gaudier, M., Kowalczykowski, S. C., and Wigley, D. B. (2004). Crystal structure of RecBCD enzyme reveals a machine for processing DNA breaks. Nature 432, 187-193.
[159] Sittidilokratna, N., Hodgson, R. A., Cowley, J. A., Jitrapakdee, S., Boonsaeng, V., Panyim, S., and Walker, P. J. (2002). Complete ORF1b-gene sequence indicates yellow head virus is an invertebrate nidovirus. Dis Aquat Organ 50, 87-93.
[160] Smith, S., Giriat, I., Schmitt, A., and de Lange, T. (1998). Tankyrase, a poly(ADP-ribose) polymerase at human telomeres. Science 282, 1484-1487.
[161] Smogorzewska, A., van Steensel, B., Bianchi, A., Oelmann, S., Schaefer, M. R., Schnapp, G., and de Lange, T. (2000). Control of human telomere length by TRF1 and TRF2. Mol Cell Biol 20, 1659-1668.
[162] Song, K., Jung, D., Jung, Y., Lee, S. G., and Lee, I. (2000). Interaction of human Ku70 with TRF2. FEBS Lett 481, 81-85.
[163] Stansel, R. M., de Lange, T., and Griffith, J. D. (2001). T-loop assembly in vitro involves binding of TRF2 near the 3' telomeric overhang. Embo J 20, 5532-5540.
[164] Stewart, S. A., Ben-Porath, I., Carey, V. J., O'Connor, B. F., Hahn, W. C., and Weinberg, R. A. (2003). Erosion of the telomeric single-strand overhang at replicative senescence. Nat Genet 33, 492-496.
[165] Suzuki, H., Chiba, T., Kobayashi, M., Takeuchi, M., Furuichi, K., and Tanaka, K. (1999). In vivo and in vitro recruitment of an IkappaBalpha-ubiquitin ligase to IkappaBalpha phosphorylated by IKK, leading to ubiquitination. Biochem Biophys Res Commun 256, 121-126.
[166] Szostak, J. W., and Blackburn, E. H. (1982). Cloning yeast telomeres on linear plasmid vectors. Cell 29, 245-255.
[167] Taggart, A. K., Teng, S. C., and Zakian, V. A. (2002). Est1p as a cell cycle-regulated activator of telomere-bound telomerase. Science 297, 1023-1026.
[168] Tanaka, H., Ryu, G. H., Seo, Y. S., Tanaka, K., Okayama, H., MacNeill, S. A., and Yuasa, Y. (2002). The fission yeast pfh1(+) gene encodes an essential 5' to 3' DNA helicase required for the completion of S-phase. Nucleic Acids Res 30, 4728-4739.
[169] Taneja, P., Gu, J., Peng, R., Carrick, R., Uchiumi, F., Ott, R. D., Gustafson, E., Podust, V. N., and Fanning, E. (2002). A dominant-negative mutant of human DNA helicase B blocks the onset of chromosomal DNA replication. J Biol Chem 277, 40853-40861.
[170] Tatusov, R. L., Koonin, E. V., and Lipman, D. J. (1997). A genomic perspective on protein families. Science 278, 631-637.
[171] Taylor, A. F., and Smith, G. R. (2003). RecBCD enzyme is a DNA helicase with fast and slow motors of opposite polarity. Nature 423, 889-893.
[172] Torres, J. Z., Schnakenberg, S. L., and Zakian, V. A. (2004). Saccharomyces cerevisiae Rrm3p DNA helicase promotes genome integrity by preventing replication fork stalling: viability of rrm3 cells requires the intra-S-phase checkpoint and fork restart activities. Mol Cell Biol 24, 3198-3212.
[173] Tuteja, N., Tuteja, R., Rahman, K., Kang, L. Y., and Falaschi, A. (1990). A DNA helicase from human cells. Nucleic Acids Res 18, 6785-6792.
[174] van Steensel, B., and de Lange, T. (1997). Control of telomere length by the human telomeric protein TRF1. Nature 385, 740-743.
[175] Veldman, T., Etheridge, K. T., and Counter, C. M. (2004). Loss of hPot1 function leads to telomere instability and a cut-like phenotype. Curr Biol 14, 2264-2270.
[176] von Kobbe, C., and Bohr, V. A. (2002). A nucleolar targeting sequence in the Werner syndrome protein resides within residues 949-1092. J Cell Sci 115, 3901-3907.
[177] Wang, W., Skopp, R., Scofield, M., and Price, C. (1992). Euplotes crassus has genes encoding telomere-binding proteins and telomere-binding protein homologs. Nucleic Acids Res 20, 6621-6629.
[178] Watson, J. D. (1972). origin of concatameric T7 DNA. Nat New Biol 239, 197-201.
[179] West, S. C. (1996). DNA helicases: new breeds of translocating motors and molecular pumps. Cell 86, 177-180.
[180] Wojciechowski, M., Fogolari, F., and Baginski, M. (2005). Thermodynamic and electrostatic properties of ternary Oxytricha nova TEBP-DNA complex. J Struct Biol 152, 169-184.
[181] Wright, W. E., Shay, J. W., and Piatyszek, M. A. (1995). Modifications of a telomeric repeat amplification protocol (TRAP) result in increased reliability, linearity and sensitivity. Nucleic Acids Res 23, 3794-3795.
[182] Wysocki, R., and Kron, S. J. (2004). Yeast cell death during DNA damage arrest is independent of caspase or reactive oxygen species. J Cell Biol 166, 311-316.
[183] Yamada, K., Yagihashi, A., Yamada, M., Asanuma, K., Moriai, R., Kobayashi, D., Tsuji, N., and Watanabe, N. (2002). Decreased gene expression for telomeric-repeat binding factors and TIN2 in malignant hematopoietic cells. Anticancer Res 22, 1315-1320.
[184] Yamada, O., Oshimi, K., and Mizoguchi, H. (1993). Telomere reduction in hematologic cells. Int J Hematol 57, 181-186.
[185] Yang, S. W., Jin, E., Chung, I. K., and Kim, W. T. (2002). Cell cycle-dependent regulation of telomerase activity by auxin, abscisic acid and protein phosphorylation in tobacco BY-2 suspension culture cells. Plant J 29, 617-626.
[186] Yao, M. C., and Yao, C. H. (1981). Repeated hexanucleotide C-C-C-C-A-A is present near free ends of macronuclear DNA of Tetrahymena. Proc Natl Acad Sci U S A 78, 7436-7439.
[187] Ye, J. Z., Hockemeyer, D., Krutchinsky, A. N., Loayza, D., Hooper, S. M., Chait, B. T., and de Lange, T. (2004). POT1-interacting protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/TRF1 complex. Genes Dev 18, 1649-1654.
[188] Young, A. C., Chavez, M., Giambernardi, T. A., Mattern, V., McGill, J. R., Harris, J. M., Sarosdy, M. F., Patel, P., and Sakaguchi, A. Y. (1997). Organization and expression of human telomere repeat binding factor genes. Somat Cell Mol Genet 23, 275-286.
[189] Yu, C. E., Oshima, J., Fu, Y. H., Wijsman, E. M., Hisama, F., Alisch, R., Matthews, S., Nakura, J., Miki, T., Ouais, S., et al. (1996). Positional cloning of the Werner's syndrome gene. Science 272, 258-262.
[190] Zakian, V. A. (1989). Structure and function of telomeres. Annu Rev Genet 23, 579-604.
[191] Zakian, V. A. (1996). Structure, function, and replication of Saccharomyces cerevisiae telomeres. Annu Rev Genet 30, 141-172.
[192] Zakian, V. A., and Pluta, A. F. (1989). Telomere formation in yeast. Nature 338, 468.
[193] Zaug, A. J., Podell, E. R., and Cech, T. R. (2005). Human POT1 disrupts telomeric G-quadruplexes allowing telomerase extension in vitro. Proc Natl Acad Sci U S A 102, 10864-10869.
[194] Zhang, D. H., Zhou, B., Huang, Y., Xu, L. X., and Zhou, J. Q. (2006). The human Pif1 helicase, a potential Escherichia coli RecD homologue, inhibits telomerase activity. Nucleic Acids Res 34, 1393-1404.
[195] Zhang P, C. S., Fu W, Mendoza M, Mattson MP. (2003). TERT suppresses apoptotis at a premitochondrial step by a mechanism requiring reverse transcriptase activity and 14-3-3 protein-binding ability. FASEB J 17, 767-769.
[196] Zhang, X., Mar, V., Zhou, W., Harrington, L., and Robinson, M. O. (1999). Telomere shortening and apoptosis in telomerase-inhibited human tumor cells. Genes Dev 13, 2388-2399.
[197] Zhou, J., Monson, E. K., Teng, S., Schulz, V. P., and Zakian, V. A. (2000). Pif1p helicase, a catalytic inhibitor of telomerase in yeast. Science 289, 771-774.
[198] Zhou, J. Q., Qi, H., Schulz, V. P., Mateyak, M. K., Monson, E. K., and Zakian, V. A. (2002). Schizosaccharomyces pombe pfh1+ encodes an essential 5' to 3' DNA helicase that is a member of the PIF1 subfamily of DNA helicases. Mol Biol Cell 13, 2180-2191.
[199] Zhou, J. Q., Tan, C. K., So, A. G., and Downey, K. M. (1996). Purification and characterization of the catalytic subunit of human DNA polymerase delta expressed in baculovirus-infected insect cells. J Biol Chem 271, 29740-29745.
[200] Zhou, X. Z., and Lu, K. P. (2001). The Pin2/TRF1-interacting protein PinX1 is a potent telomerase inhibitor. Cell 107, 347-359.
[201] Zhu, J., Wang, H., Bishop, J. M., and Blackburn, E. H. (1999). Telomerase extends the lifespan of virus-transformed human cells without net telomere lengthening. Proc Natl Acad Sci U S A 96, 3723-3728.
[2] Akimov, S. S., Ramezani, A., Hawley, T. S., and Hawley, R. G. (2005). Bypass of senescence, immortalization, and transformation of human hematopoietic progenitor cells. Stem Cells 23, 1423-1433.
[3] Akiyama, Y., Maesawa, C., Wada, K., Fujisawa, K., Itabashi, T., Noda, Y., Honda, T., Sato, N., Ishida, K., Takagane, A., et al. (2004). Human PinX1, a potent telomerase inhibitor, is not involved in human gastrointestinal tract carcinoma. Oncol Rep 11, 871-874.
[4] Allshire, R. C., Gosden, J. R., Cross, S. H., Cranston, G., Rout, D., Sugawara, N., Szostak, J. W., Fantes, P. A., and Hastie, N. D. (1988). Telomeric repeat from T. thermophila cross hybridizes with human telomeres. Nature 332, 656-659.
[5] Amundsen, S. K., Taylor, A. F., and Smith, G. R. (2002). A domain of RecC required for assembly of the regulatory RecD subunit into the Escherichia coli RecBCD holoenzyme. Genetics 161, 483-492.
[6] Anderson, E. M., Halsey, W. A., and Wuttke, D. S. (2002). Delineation of the high-affinity single-stranded telomeric DNA-binding domain of Saccharomyces cerevisiae Cdc13. Nucleic Acids Res 30, 4305-4313.
[7] Armbruster, B. N., Linardic, C. M., Veldman, T., Bansal, N. P., Downie, D. L., and Counter, C. M. (2004). Rescue of an hTERT mutant defective in telomere elongation by fusion with hPot1. Mol Cell Biol 24, 3552-3561.
[8] Backer, J., and Foury, F. (1985). Repair properties in yeast mitochondrial DNA mutators. Curr Genet 10, 7-13.
[9] Banik, S. S., and Counter, C. M. (2004). Characterization of interactions between PinX1 and human telomerase subunits hTERT and hTR. J Biol Chem.
[10] Baroin, A., Prat, A., and Caron, F. (1987). Telomeric site position heterogeneity in macronuclear DNA of Paramecium primaurelia. Nucleic Acids Res 15, 1717-1728.
[11] Baumann, P., Podell, E., and Cech, T. R. (2002). Human Pot1 (protection of telomeres) protein: cytolocalization, gene structure, and alternative splicing. Mol Cell Biol 22, 8079-8087.
[12] Bessler, J. B., Torredagger, J. Z., and Zakian, V. A. (2001). The Pif1p subfamily of helicases: region-specific DNA helicases? Trends Cell Biol 11, 60-65.
[13] Bhattacharyya, S., and Lahue, R. S. (2005). Srs2 helicase of Saccharomyces cerevisiae selectively unwinds triplet repeat DNA. J Biol Chem 280, 33311-33317.
[14] Bilaud, T., Brun, C., Ancelin, K., Koering, C. E., Laroche, T., and Gilson, E. (1997). Telomeric localization of TRF2, a novel human telobox protein. Nat Genet 17, 236-239.
[15] Blackburn, E. H. (1990a). Telomeres and their synthesis. Harvey Lect 86, 1-18.
[16] Blackburn, E. H. (1990b). Telomeres: structure and synthesis. J Biol Chem 265, 5919-5921.
[17] 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.
[18] Blasco, M. A. (2003). Mammalian telomeres and telomerase: why they matter for cancer and aging. Eur J Cell Biol 82, 441-446.
[19] Boltze, C., Lehnert, H., Schneider-Stock, R., Peters, B., Hoang Vu, C., and Roessner, A. (2004). Withdrawal. HSP90 is a key for telomerase activation and malignant transition in pheochromocytoma. Endocrine 23, 229.
[20] Boule, J. B., Vega, L. R., and Zakian, V. A. (2005). The yeast Pif1p helicase removes telomerase from telomeric DNA. Nature.
[21] Boveri, T. (1887). ber Differenzierung der Zellkerne wthrend der Fiirchung des
[22] Eies von Ascaris megalocephala. Anat Ariz 2, 688-693.
[23] Broccoli, D., Smogorzewska, A., Chong, L., and de Lange, T. (1997). Human telomeres contain two distinct Myb-related proteins, TRF1 and TRF2. Nat Genet 17, 231-235.
[24] 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.
[25] 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.
[26] Buczek, P., Orr, R. S., Pyper, S. R., Shum, M., Kimmel, E., Ota, I., Gerum, S. E., and Horvath, M. P. (2005). Binding linkage in a telomere DNA-protein complex at the ends of Oxytricha nova chromosomes. J Mol Biol 350, 938-952.
[27] Budarf, M. L., and Blackburn, E. H. (1986). Chromatin structure of the telomeric region and 3'-nontranscribed spacer of Tetrahymena ribosomal RNA genes. J Biol Chem 261, 363-369.
[28] Budd, M. E., Choe, W., and Campbell, J. L. (2000). The nuclease activity of the yeast DNA2 protein, which is related to the RecB-like nucleases, is essential in vivo. J Biol Chem 275, 16518-16529.
[29] Budd, M. E., Reis, C. C., Smith, S., Myung, K., and Campbell, J. L. (2006). Evidence suggesting that Pif1 helicase functions in DNA replication with the Dna2 helicase/nuclease and DNA polymerase delta. Mol Cell Biol 26, 2490-2500.
[30] Burma, S., and Chen, D. J. (2004). Role of DNA-PK in the cellular response to DNA double-strand breaks. DNA Repair (Amst) 3, 909-918.
[31] Chai, W., Ford, L. P., Lenertz, L., Wright, W. E., and Shay, J. W. (2002). Human Ku70/80 associates physically with telomerase through interaction with hTERT. J Biol Chem 277, 47242-47247.
[32] Chang, W., Dynek, J. N., and Smith, S. (2003). TRF1 is degraded by ubiquitin-mediated proteolysis after release from telomeres. Genes Dev 17, 1328-1333.
[33] Chong, L., van Steensel, B., Broccoli, D., Erdjument-Bromage, H., Hanish, J., Tempst, P., and de Lange, T. (1995). A human telomeric protein. Science 270, 1663-1667.
[34] Classen, S., Ruggles, J. A., and Schultz, S. C. (2001). Crystal structure of the N-terminal domain of Oxytricha nova telomere end-binding protein alpha subunit both uncomplexed and complexed with telomeric ssDNA. J Mol Biol 314, 1113-1125.
[35] Cohen, H., and Sinclair, D. A. (2001). Recombination-mediated lengthening of terminal telomeric repeats requires the Sgs1 DNA helicase. Proc Natl Acad Sci U S A 98, 3174-3179.
[36] Colgin, L. M., Baran, K., Baumann, P., Cech, T. R., and Reddel, R. R. (2003). Human POT1 facilitates telomere elongation by telomerase. Curr Biol 13, 942-946.
[37] Colgin, L. M., Wilkinson, C., Englezou, A., Kilian, A., Robinson, M. O., and Reddel, R. R. (2000). The hTERTalpha splice variant is a dominant negative inhibitor of telomerase activity. Neoplasia 2, 426-432.
[38] Cooper, J. P., Nimmo, E. R., Allshire, R. C., and Cech, T. R. (1997). Regulation of telomere length and function by a Myb-domain protein in fission yeast. Nature 385, 744-747.
[39] Counter, C. M., Avilion, A. A., LeFeuvre, C. E., Stewart, N. G., Greider, C. W., Harley, C. B., and Bacchetti, S. (1992). Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity. Embo J 11, 1921-1929.
[40] Counter, C. M., Hahn, W. C., Wei, W., Caddle, S. D., Beijersbergen, R. L., Lansdorp, P. M., Sedivy, J. M., and Weinberg, R. A. (1998). Dissociation among in vitro telomerase activity, telomere maintenance, and cellular immortalization. Proc Natl Acad Sci U S A 95, 14723-14728.
[41] Cowell, J. K., and Miller, O. J. (1983). Occurrence and evolution of homogeneously staining regions may be due to breakage-fusion-bridge cycles following telomere loss. Chromosoma 88, 216-221.
[42] Crabbe, L., Verdun, R. E., Haggblom, C. I., and Karlseder, J. (2004). Defective telomere lagging strand synthesis in cells lacking WRN helicase activity. Science 306, 1951-1953.
[43] d'Adda di Fagagna, F., Teo, S. H., and Jackson, S. P. (2004). Functional links between telomeres and proteins of the DNA-damage response. Genes Dev 18, 1781-1799.
[44] Dawson, D., and Herrick, G. (1984). Telomeric properties of C4A4-homologous sequences in micronuclear DNA of Oxytricha fallax. Cell 36, 171-177.
[45] de Lange, T. (1992). Human telomeres are attached to the nuclear matrix. Embo J 11, 717-724.
[46] de Lange, T., Shiue, L., Myers, R. M., Cox, D. R., Naylor, S. L., Killery, A. M., and Varmus, H. E. (1990). Structure and variability of human chromosome ends. Mol Cell Biol 10, 518-527.
[47] Debabov, V. G. (1979). [DNA unwinding proteins]. Usp Sovrem Biol 87, 170-184.
[48] Deloukas, P., Schuler, G. D., Gyapay, G., Beasley, E. M., Soderlund, C., Rodriguez-Tome, P., Hui, L., Matise, T. C., McKusick, K. B., Beckmann, J. S., et al. (1998). A physical map of 30,000 human genes. Science 282, 744-746.
[49] Dermic, D. (2006). Functions of multiple exonucleases are essential for cell viability, DNA repair and homologous recombination in recD mutants of Escherichia coli. Genetics.
[50] Dermic, D., Halupecki, E., Zahradka, D., and Petranovic, M. (2005). RecBCD enzyme overproduction impairs DNA repair and homologous recombination in Escherichia coli. Res Microbiol 156, 304-311.
[51] Dettlaff-Pokora, A., and Schlichtholz, B. (2003). [Alternative lengthening of telomeres]. Postepy Biochem 49, 147-156.
[52] Dhar, S., Squire, J. A., Hande, M. P., Wellinger, R. J., and Pandita, T. K. (2000). Inactivation of 14-3-3sigma influences telomere behavior and ionizing radiation-induced chromosomal instability. Mol Cell Biol 20, 7764-7772.
[53] Dillingham, M. S., Spies, M., and Kowalczykowski, S. C. (2003). RecBCD enzyme is a bipolar DNA helicase. Nature 423, 893-897.
[54] Dillingham, M. S., Webb, M. R., and Kowalczykowski, S. C. (2005). Bipolar DNA translocation contributes to highly processive DNA unwinding by RecBCD enzyme. J Biol Chem 280, 37069-37077.
[55] Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., Pereira-Smith, O., and et al. (1995). A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci U S A 92, 9363-9367.
[56] Du, X., Shen, J., Kugan, N., Furth, E. E., Lombard, D. B., Cheung, C., Pak, S., Luo, G., Pignolo, R. J., DePinho, R. A., et al. (2004). Telomere shortening exposes functions for the mouse Werner and Bloom syndrome genes. Mol Cell Biol 24, 8437-8446.
[57] Eitner, G., Solonin, A. S., and Tanyashin, V. I. (1981). Cloning of a recA-like gene of Proteus mirabilis. Gene 14, 301-308.
[58] Ellis, N. A., Groden, J., Ye, T. Z., Straughen, J., Lennon, D. J., Ciocci, S., Proytcheva, M., and German, J. (1995). The Bloom's syndrome gene product is homologous to RecQ helicases. Cell 83, 655-666.
[59] Emery, H. S., and Weiner, A. M. (1981). An irregular satellite sequence is found at the termini of the linear extrachromosomal rDNA in Dictyostelium discoideum. Cell 26, 411-419.
[60] Fang, G., and Cech, T. R. (1993). The beta subunit of Oxytricha telomere-binding protein promotes G-quartet formation by telomeric DNA. Cell 74, 875-885.
[61] Fisher, T. S., and Zakian, V. A. (2005). Ku: A multifunctional protein involved in telomere maintenance. DNA Repair (Amst).
[62] Ford, L. P., Wright, W. E., and Shay, J. W. (2002). A model for heterogeneous nuclear ribonucleoproteins in telomere and telomerase regulation. Oncogene 21, 580-583.
[63] Forney, J., Henderson, E. R., and Blackburn, E. H. (1987). Identification of the telomeric sequence of the acellular slime molds Didymium iridis and Physarum polycephalum. Nucleic Acids Res 15, 9143-9152.
[64] Forney, J. D., and Blackburn, E. H. (1988). Developmentally controlled telomere addition in wild-type and mutant paramecia. Mol Cell Biol 8, 251-258.
[65] Forsythe, H. L., Elmore, L. W., Jensen, K. O., Landon, M. R., and Holt, S. E. (2002). Retroviral-mediated expression of telomerase in normal human cells provides a selective growth advantage. Int J Oncol 20, 1137-1143.
[66] Foury, F., and Kolodynski, J. (1983). pif mutation blocks recombination between mitochondrial rho+ and rho-genomes having tandemly arrayed repeat units in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 80, 5345-5349.
[67] Foury, F., and Lahaye, A. (1987). Cloning and sequencing of the PIF gene involved in repair and recombination of yeast mitochondrial DNA. Embo J 6, 1441-1449.
[68] Frank-Vaillant, M., and Marcand, S. (2001). NHEJ regulation by mating type is exercised through a novel protein, Lif2p, essential to the ligase IV pathway. Genes Dev 15, 3005-3012.
[69] George, J. W., Ghate, S., Matson, S. W., and Besterman, J. M. (1992). Inhibition of DNA helicase II unwinding and ATPase activities by DNA-interacting ligands. Kinetics and specificity. J Biol Chem 267, 10683-10689.
[70] Gonzalez, I. L., Petersen, R., and Sylvester, J. E. (1989). Independent insertion of Alu elements in the human ribosomal spacer and their concerted evolution. Mol Biol Evol 6, 413-423.
[71] Gorbalenya, A. E., Koonin, E. V., Donchenko, A. P., and Blinov, V. M. (1989). Two related superfamilies of putative helicases involved in replication, recombination, repair and expression of DNA and RNA genomes. Nucleic Acids Res 17, 4713-4730.
[72] Gray, J. T., Celander, D. W., Price, C. M., and Cech, T. R. (1991). Cloning and expression of genes for the Oxytricha telomere-binding protein: specific subunit interactions in the telomeric complex. Cell 67, 807-814.
[73] Greider, C. W. (1999). Telomeres do D-loop-T-loop. Cell 97, 419-422.
[74] Greider, C. W., and Blackburn, E. H. (1985). Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell 43, 405-413.
[75] Gu, J., Xia, X., Yan, P., Liu, H., Podust, V. N., Reynolds, A. B., and Fanning, E. (2004). Cell cycle-dependent regulation of a human DNA helicase that localizes in DNA damage foci. Mol Biol Cell 15, 3320-3332.
[76] H. J. Muller, S., 84 . (1927). Science 46, 84.
[77] Harley, C. B., and Kim, N. W. (1996). Telomerase and cancer. Important Adv Oncol, 57-67.
[78] Hayakawa, S., Kaneko, H., Fukao, T., Kasahara, K., Matsumoto, T., Furuichi, Y., and Kondo, N. (2000). Characterization of the nuclear localization signal in the DNA helicase responsible for Bloom syndrome. Int J Mol Med 5, 477-484.
[79] Heacock, M., Spangler, E., Riha, K., Puizina, J., and Shippen, D. E. (2004). Molecular analysis of telomere fusions in Arabidopsis: multiple pathways for chromosome end-joining. Embo J 23, 2304-2313.
[80] Higashibata, H., Kikuchi, H., Kawarabayasi, Y., and Matsui, I. (2003). Helicase and nuclease activities of hyperthermophile Pyrococcus horikoshii Dna2 inhibited by substrates with RNA segments at 5'-end. J Biol Chem 278, 15983-15990.
[81] 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.
[82] Hotta, Y., and Stern, H. (1978). DNA unwinding protein from meiotic cells of Lilium. Biochemistry 17, 1872-1880.
[83] Hsu, H. L., Gilley, D., Blackburn, E. H., and Chen, D. J. (1999). Ku is associated with the telomere in mammals. Proc Natl Acad Sci U S A 96, 12454-12458.
[84] Huang, P., Pryde, F. E., Lester, D., Maddison, R. L., Borts, R. H., Hickson, I. D., and Louis, E. J. (2001). SGS1 is required for telomere elongation in the absence of telomerase. Curr Biol 11, 125-129.
[85] Ivessa, A. S., Zhou, J. Q., Schulz, V. P., Monson, E. K., and Zakian, V. A. (2002). Saccharomyces Rrm3p, a 5' to 3' DNA helicase that promotes replication fork progression through telomeric and subtelomeric DNA. Genes Dev 16, 1383-1396.
[86] Ivessa, A. S., Zhou, J. Q., and Zakian, V. A. (2000). The Saccharomyces Pif1p DNA helicase and the highly related Rrm3p have opposite effects on replication fork progression in ribosomal DNA. Cell 100, 479-489.
[87] Johnson, F. B., Marciniak, R. A., McVey, M., Stewart, S. A., Hahn, W. C., and Guarente, L. (2001). The Saccharomyces cerevisiae WRN homolog Sgs1p participates in telomere maintenance in cells lacking telomerase. Embo J 20, 905-913.
[88] Kaminker, P. G., Kim, S. H., Taylor, R. D., Zebarjadian, Y., Funk, W. D., Morin, G. B., Yaswen, P., and Campisi, J. (2001). TANK2, a new TRF1-associated poly(ADP-ribose) polymerase, causes rapid induction of cell death upon overexpression. J Biol Chem 276, 35891-35899.
[89] Kartalou, M., and Essigmann, J. M. (2001). Recognition of cisplatin adducts by cellular proteins. Mutat Res 478, 1-21.
[90] Kim, J. H., Park, S. M., Kang, M. R., Oh, S. Y., Lee, T. H., Muller, M. T., and Chung, I. K. (2005). Ubiquitin ligase MKRN1 modulates telomere length homeostasis through a proteolysis of hTERT. Genes Dev 19, 776-781.
[91] 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.
[92] Kim, S. H., Kaminker, P., and Campisi, J. (1999). TIN2, a new regulator of telomere length in human cells. Nat Genet 23, 405-412.
[93] Kimura, A., Ohmichi, M., Kawagoe, J., Kyo, S., Mabuchi, S., Takahashi, T., Ohshima, C., Arimoto-Ishida, E., Nishio, Y., Inoue, M., et al. (2004). Induction of hTERT expression and phosphorylation by estrogen via Akt cascade in human ovarian cancer cell lines. Oncogene 23, 4505-4515.
[94] Kishi, S., Wulf, G., Nakamura, M., and Lu, K. P. (2001). Telomeric protein Pin2/TRF1 induces mitotic entry and apoptosis in cells with short telomeres and is down-regulated in human breast tumors. Oncogene 20, 1497-1508.
[95] Kitao, S., Shimamoto, A., Goto, M., Miller, R. W., Smithson, W. A., Lindor, N. M., and Furuichi, Y. (1999). Mutations in RECQL4 cause a subset of cases of Rothmund-Thomson syndrome. Nat Genet 22, 82-84.
[96] Klapper, W., Krams, M., Qian, W., Janssen, D., and Parwaresch, R. (2003). Telomerase activity in B-cell non-Hodgkin lymphomas is regulated by hTERT transcription and correlated with telomere-binding protein expression but uncoupled from proliferation. Br J Cancer 89, 713-719.
[97] Klobutcher, L. A., Swanton, M. T., Donini, P., and Prescott, D. M. (1981). All gene-sized DNA molecules in four species of hypotrichs have the same terminal sequence and an unusual 3' terminus. Proc Natl Acad Sci U S A 78, 3015-3019.
[98] Kramer, K. M., and Haber, J. E. (1993). New telomeres in yeast are initiated with a highly selected subset of TG1-3 repeats. Genes Dev 7, 2345-2356.
[99] Lahaye, A., Leterme, S., and Foury, F. (1993a). PIF1 DNA helicase from Saccharomyces cerevisiae. Biochemical characterization of the enzyme. J Biol Chem 268, 26155-26161.
[100] Lahaye, A., Leterme, S., and Foury, F. (1993b). PIF1 DNA helicase from Saccharomyces cerevisiae. Biochemical characterization of the enzyme. J Biol Chem 268, 26155-26161.
[101] Lahaye, A., Stahl, H., Thines-Sempoux, D., and Foury, F. (1991). PIF1: a DNA helicase in yeast mitochondria. Embo J 10, 997-1007.
[102] Lahaye, A., Stahl, H., Thines, S. D., and Foury, F (1991). PIF1: a DNA helicase in yeast mitochondria. Embo J 10, 997-1007.
[103] Lee, J. W., Harrigan, J., Opresko, P. L., and Bohr, V. A. (2005). Pathways and functions of the Werner syndrome protein. Mech Ageing Dev 126, 79-86.
[104] Lei, M., Podell, E. R., and Cech, T. R. (2004). Structure of human POT1 bound to telomeric single-stranded DNA provides a model for chromosome end-protection. Nat Struct Mol Biol 11, 1223-1229.
[105] Lei, M., Zaug, A. J., Podell, E. R., and Cech, T. R. (2005). Switching human telomerase on and off with hPOT1 protein in vitro. J Biol Chem.
[106] Li, B., and de Lange, T. (2003). Rap1 affects the length and heterogeneity of human telomeres. Mol Biol Cell 14, 5060-5068.
[107] Li, B., Oestreich, S., and de Lange, T. (2000). Identification of human Rap1: implications for telomere evolution. Cell 101, 471-483.
[108] Lin, Y. C., Shih, J. W., Hsu, C. L., and Lin, J. J. (2001). Binding and partial denaturing of G-quartet DNA by Cdc13p of Saccharomyces cerevisiae. J Biol Chem 276, 47671-47674.
[109] Lingner, J., and Cech, T. R. (1998). Telomerase and chromosome end maintenance. Curr Opin Genet Dev 8, 226-232.
[110] Liu, D., O'Connor, M. S., Qin, J., and Songyang, Z. (2004). Telosome --A mammalian telomere associated complex formed by multiple telomeric proteins. J Biol Chem.
[111] Loayza, D., and De Lange, T. (2003). POT1 as a terminal transducer of TRF1 telomere length control. Nature 423, 1013-1018.
[112] Lohman, T. M., and Bjornson, K. P. (1996). Mechanisms of helicase-catalyzed DNA unwinding. Annu Rev Biochem 65, 169-214.
[113] Lundblad, V., and Blackburn, E. H. (1993). An alternative pathway for yeast telomere maintenance rescues est1-senescence. Cell 73, 347-360.
[114] Lustig, A. J. (2001). Cdc13 subcomplexes regulate multiple telomere functions. Nat Struct Biol 8, 297-299.
[115] Machwe, A., Xiao, L., and Orren, D. K. (2006). Length-dependent degradation of single-stranded 3' ends by the Werner syndrome protein (WRN): implications for spatial orientation and coordinated 3' to 5' movement of its ATPase/helicase and exonuclease domains. BMC Mol Biol 7, 6.
[116] Marcand, S., Gilson, E., and Shore, D. (1997). A protein-counting mechanism for telomere length regulation in yeast. Science 275, 986-990.
[117] Marchler-Bauer, A., and Bryant, S. H. (2004). CD-Search: protein domain annotations on the fly. Nucleic Acids Res 32, W327-331.
[118] Matson, S. W. (1991). DNA helicases of Escherichia coli. Prog Nucleic Acid Res Mol Biol 40, 289-326.
[119] Matson, S. W., and Kaiser-Rogers, K. A. (1990). DNA helicases. Annu Rev Biochem 59, 289-329.
[120] Matsumoto, T., Fukui, K., Niwa, O., Sugawara, N., Szostak, J. W., and Yanagida, M. (1987). Identification of healed terminal DNA fragments in linear minichromosomes of Schizosaccharomyces pombe. Mol Cell Biol 7, 4424-4430.
[121] Matsutani, N., Yokozaki, H., Tahara, E., Tahara, H., Kuniyasu, H., Kitadai, Y., Haruma, K., Chayama, K., and Yasui, W. (2001). Expression of MRE11 complex (MRE11, RAD50, NBS1) and hRap1 and its relation with telomere regulation, telomerase activity in human gastric carcinomas. Pathobiology 69, 219-224.
[122] Mattern, K. A., Swiggers, S. J., Nigg, A. L., Lowenberg, B., Houtsmuller, A. B., and Zijlmans, J. M. (2004). Dynamics of protein binding to telomeres in living cells: implications for telomere structure and function. Mol Cell Biol 24, 5587-5594.
[123] McClintock, B. (1941). The stability of broken ends of chromosomes in Zea mays. Genetics 26, 234?282.
[124] McEachern, M. J., Krauskopf, A., and Blackburn, E. H. (2000). Telomeres and their control. Annu Rev Genet 34, 331-358.
[125] Meyerson, M. (1998). Telomerase enzyme activation and human cell immortalization. Toxicol Lett 102-103, 41-45.
[126] Meyne, J., Ratliff, R. L., and Moyzis, R. K. (1989). Conservation of the human telomere sequence (TTAGGG)n among vertebrates. Proc Natl Acad Sci U S A 86, 7049-7053.
[127] 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 Cdc13. J Mol Biol 338, 241-255.
[128] Mohanty, B. K., Bairwa, N. K., and Bastia, D. (2006). The Tof1p-Csm3p protein complex counteracts the Rrm3p helicase to control replication termination of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 103, 897-902.
[129] Morin, G. B. (1989). The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesizes TTAGGG repeats. Cell 59, 521-529.
[130] 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.
[131] Muller, B., Boehmer, P. E., Emmerson, P. T., and West, S. C. (1991). Action of RecBCD enzyme on Holliday structures made by RecA. J Biol Chem 266, 19028-19033.
[132] Muller, H. (1938). The remaking of chromosomes. Collecting Net , 8.
[133] Nakamura, M., Zhou, X. Z., Kishi, S., Kosugi, I., Tsutsui, Y., and Lu, K. P. (2001). A specific interaction between the telomeric protein Pin2/TRF1 and the mitotic spindle. Curr Biol 11, 1512-1516.
[134] O'Connor, M. S., Safari, A., Liu, D., Qin, J., and Songyang, Z. (2004). The human Rap1 protein complex and modulation of telomere length. J Biol Chem 279, 28585-28591.
[135] O'Rourke, T. W., Doudican, N. A., Zhang, H., Eaton, J. S., Doetsch, P. W., and Shadel, G. S. (2005). Differential involvement of the related DNA helicases Pif1p and Rrm3p in mtDNA point mutagenesis and stability. Gene 354, 86-92.
[136] Ogawa, T., Shinohara, A., Nabetani, A., Ikeya, T., Yu, X., Egelman, E. H., and Ogawa, H. (1993). RecA-like recombination proteins in eukaryotes: functions and structures of RAD51 genes. Cold Spring Harb Symp Quant Biol 58, 567-576.
[137] Oka, Y., Shiota, S., Nakai, S., Nishida, Y., and Okubo, S. (1980). Inverted terminal repeat sequence in the macronuclear DNA of Stylonychia pustulata. Gene 10, 301-306.
[138] Opresko, P. L., Otterlei, M., Graakjaer, J., Bruheim, P., Dawut, L., Kolvraa, S., May, A., Seidman, M. M., and Bohr, V. A. (2004). The Werner Syndrome Helicase and Exonuclease Cooperate to Resolve Telomeric D Loops in a Manner Regulated by TRF1 and TRF2. Mol Cell 14, 763-774.
[139] Opresko, P. L., von Kobbe, C., Laine, J. P., Harrigan, J., Hickson, I. D., and Bohr, V. A. (2002). Telomere-binding protein TRF2 binds to and stimulates the Werner and Bloom syndrome helicases. J Biol Chem 277, 41110-41119.
[140] Paeschke, K., Simonsson, T., Postberg, J., Rhodes, D., and Lipps, H. J. (2005). Telomere end-binding proteins control the formation of G-quadruplex DNA structures in vivo. Nat Struct Mol Biol 12, 847-854.
[141] Palmbos, P. L., Daley, J. M., and Wilson, T. E. (2005). Mutations of the Yku80 C terminus and Xrs2 FHA domain specifically block yeast nonhomologous end joining. Mol Cell Biol 25, 10782-10790.
[142] Patel, S. S., and Picha, K. M. (2000). Structure and function of hexameric helicases. Annu Rev Biochem 69, 651-697.
[143] Peersen, O. B., Ruggles, J. A., and Schultz, S. C. (2002). Dimeric structure of the Oxytricha nova telomere end-binding protein alpha-subunit bound to ssDNA. Nat Struct Biol 9, 182-187.
[144] Phillips, R. J., Hickleton, D. C., Boehmer, P. E., and Emmerson, P. T. (1997). The RecB protein of Escherichia coli translocates along single-stranded DNA in the 3' to 5' direction: a proposed ratchet mechanism. Mol Gen Genet 254, 319-329.
[145] Pluta, A. F., Kaine, B. P., and Spear, B. B. (1982). The terminal organization of macronuclear DNA in Oxytricha fallax. Nucleic Acids Res 10, 8145-8154.
[146] Richards, E. J., and Ausubel, F. M. (1988). Isolation of a higher eukaryotic telomere from Arabidopsis thaliana. Cell 53, 127-136.
[147] Rigden, D. J. (2005). An inactivated nuclease-like domain in RecC with novel function: implications for evolution. BMC Struct Biol 5, 9.
[148] Ryu, G. H., Tanaka, H., Kim, D. H., Kim, J. H., Bae, S. H., Kwon, Y. N., Rhee, J. S., MacNeill, S. A., and Seo, Y. S. (2004). Genetic and biochemical analyses of Pfh1 DNA helicase function in fission yeast. Nucleic Acids Res 32, 4205-4216.
[149] Salaj-Smic, E., Dermic, D., Brcic-Kostic, K., Cajo, G. C., and Trgovcevic, E. (2000). In vivo studies of the Escherichia coli RecB polypeptide lacking its nuclease center. Res Microbiol 151, 769-776.
[150] Sanchez-Alonso, P., and Guzman, P. (1998). Organization of chromosome ends in Ustilago maydis. RecQ-like helicase motifs at telomeric regions. Genetics 148, 1043-1054.
[151] Sandell, L. L., and Zakian, V. A. (1993). Loss of a yeast telomere: arrest, recovery, and chromosome loss. Cell 75, 729-739.
[152] Schulz, V. P., and Zakian, V. A. (1994). The saccharomyces PIF1 DNA helicase inhibits telomere elongation and de novo telomere formation. Cell 76, 145-155.
[153] Seimiya, H., Sawada, H., Muramatsu, Y., Shimizu, M., Ohko, K., Yamane, K., and Tsuruo, T. (2000). Involvement of 14-3-3 proteins in nuclear localization of telomerase. Embo J 19, 2652-2661.
[154] Shampay, J., Szostak, J. W., and Blackburn, E. H. (1984). DNA sequences of telomeres maintained in yeast. Nature 310, 154-157.
[155] Shen, M., Haggblom, C., Vogt, M., Hunter, T., and Lu, K. P. (1997). Characterization and cell cycle regulation of the related human telomeric proteins Pin2 and TRF1 suggest a role in mitosis. Proc Natl Acad Sci U S A 94, 13618-13623.
[156] Shinohara, A., Ogawa, H., and Ogawa, T. (1992). Rad51 protein involved in repair and recombination in S. cerevisiae is a RecA-like protein. Cell 69, 457-470.
[157] Simonsson, T. (2001). The human TINF2 gene organisation and chromosomal localization. Biochimie 83, 433-435.
[158] Singleton, M. R., Dillingham, M. S., Gaudier, M., Kowalczykowski, S. C., and Wigley, D. B. (2004). Crystal structure of RecBCD enzyme reveals a machine for processing DNA breaks. Nature 432, 187-193.
[159] Sittidilokratna, N., Hodgson, R. A., Cowley, J. A., Jitrapakdee, S., Boonsaeng, V., Panyim, S., and Walker, P. J. (2002). Complete ORF1b-gene sequence indicates yellow head virus is an invertebrate nidovirus. Dis Aquat Organ 50, 87-93.
[160] Smith, S., Giriat, I., Schmitt, A., and de Lange, T. (1998). Tankyrase, a poly(ADP-ribose) polymerase at human telomeres. Science 282, 1484-1487.
[161] Smogorzewska, A., van Steensel, B., Bianchi, A., Oelmann, S., Schaefer, M. R., Schnapp, G., and de Lange, T. (2000). Control of human telomere length by TRF1 and TRF2. Mol Cell Biol 20, 1659-1668.
[162] Song, K., Jung, D., Jung, Y., Lee, S. G., and Lee, I. (2000). Interaction of human Ku70 with TRF2. FEBS Lett 481, 81-85.
[163] Stansel, R. M., de Lange, T., and Griffith, J. D. (2001). T-loop assembly in vitro involves binding of TRF2 near the 3' telomeric overhang. Embo J 20, 5532-5540.
[164] Stewart, S. A., Ben-Porath, I., Carey, V. J., O'Connor, B. F., Hahn, W. C., and Weinberg, R. A. (2003). Erosion of the telomeric single-strand overhang at replicative senescence. Nat Genet 33, 492-496.
[165] Suzuki, H., Chiba, T., Kobayashi, M., Takeuchi, M., Furuichi, K., and Tanaka, K. (1999). In vivo and in vitro recruitment of an IkappaBalpha-ubiquitin ligase to IkappaBalpha phosphorylated by IKK, leading to ubiquitination. Biochem Biophys Res Commun 256, 121-126.
[166] Szostak, J. W., and Blackburn, E. H. (1982). Cloning yeast telomeres on linear plasmid vectors. Cell 29, 245-255.
[167] Taggart, A. K., Teng, S. C., and Zakian, V. A. (2002). Est1p as a cell cycle-regulated activator of telomere-bound telomerase. Science 297, 1023-1026.
[168] Tanaka, H., Ryu, G. H., Seo, Y. S., Tanaka, K., Okayama, H., MacNeill, S. A., and Yuasa, Y. (2002). The fission yeast pfh1(+) gene encodes an essential 5' to 3' DNA helicase required for the completion of S-phase. Nucleic Acids Res 30, 4728-4739.
[169] Taneja, P., Gu, J., Peng, R., Carrick, R., Uchiumi, F., Ott, R. D., Gustafson, E., Podust, V. N., and Fanning, E. (2002). A dominant-negative mutant of human DNA helicase B blocks the onset of chromosomal DNA replication. J Biol Chem 277, 40853-40861.
[170] Tatusov, R. L., Koonin, E. V., and Lipman, D. J. (1997). A genomic perspective on protein families. Science 278, 631-637.
[171] Taylor, A. F., and Smith, G. R. (2003). RecBCD enzyme is a DNA helicase with fast and slow motors of opposite polarity. Nature 423, 889-893.
[172] Torres, J. Z., Schnakenberg, S. L., and Zakian, V. A. (2004). Saccharomyces cerevisiae Rrm3p DNA helicase promotes genome integrity by preventing replication fork stalling: viability of rrm3 cells requires the intra-S-phase checkpoint and fork restart activities. Mol Cell Biol 24, 3198-3212.
[173] Tuteja, N., Tuteja, R., Rahman, K., Kang, L. Y., and Falaschi, A. (1990). A DNA helicase from human cells. Nucleic Acids Res 18, 6785-6792.
[174] van Steensel, B., and de Lange, T. (1997). Control of telomere length by the human telomeric protein TRF1. Nature 385, 740-743.
[175] Veldman, T., Etheridge, K. T., and Counter, C. M. (2004). Loss of hPot1 function leads to telomere instability and a cut-like phenotype. Curr Biol 14, 2264-2270.
[176] von Kobbe, C., and Bohr, V. A. (2002). A nucleolar targeting sequence in the Werner syndrome protein resides within residues 949-1092. J Cell Sci 115, 3901-3907.
[177] Wang, W., Skopp, R., Scofield, M., and Price, C. (1992). Euplotes crassus has genes encoding telomere-binding proteins and telomere-binding protein homologs. Nucleic Acids Res 20, 6621-6629.
[178] Watson, J. D. (1972). origin of concatameric T7 DNA. Nat New Biol 239, 197-201.
[179] West, S. C. (1996). DNA helicases: new breeds of translocating motors and molecular pumps. Cell 86, 177-180.
[180] Wojciechowski, M., Fogolari, F., and Baginski, M. (2005). Thermodynamic and electrostatic properties of ternary Oxytricha nova TEBP-DNA complex. J Struct Biol 152, 169-184.
[181] Wright, W. E., Shay, J. W., and Piatyszek, M. A. (1995). Modifications of a telomeric repeat amplification protocol (TRAP) result in increased reliability, linearity and sensitivity. Nucleic Acids Res 23, 3794-3795.
[182] Wysocki, R., and Kron, S. J. (2004). Yeast cell death during DNA damage arrest is independent of caspase or reactive oxygen species. J Cell Biol 166, 311-316.
[183] Yamada, K., Yagihashi, A., Yamada, M., Asanuma, K., Moriai, R., Kobayashi, D., Tsuji, N., and Watanabe, N. (2002). Decreased gene expression for telomeric-repeat binding factors and TIN2 in malignant hematopoietic cells. Anticancer Res 22, 1315-1320.
[184] Yamada, O., Oshimi, K., and Mizoguchi, H. (1993). Telomere reduction in hematologic cells. Int J Hematol 57, 181-186.
[185] Yang, S. W., Jin, E., Chung, I. K., and Kim, W. T. (2002). Cell cycle-dependent regulation of telomerase activity by auxin, abscisic acid and protein phosphorylation in tobacco BY-2 suspension culture cells. Plant J 29, 617-626.
[186] Yao, M. C., and Yao, C. H. (1981). Repeated hexanucleotide C-C-C-C-A-A is present near free ends of macronuclear DNA of Tetrahymena. Proc Natl Acad Sci U S A 78, 7436-7439.
[187] Ye, J. Z., Hockemeyer, D., Krutchinsky, A. N., Loayza, D., Hooper, S. M., Chait, B. T., and de Lange, T. (2004). POT1-interacting protein PIP1: a telomere length regulator that recruits POT1 to the TIN2/TRF1 complex. Genes Dev 18, 1649-1654.
[188] Young, A. C., Chavez, M., Giambernardi, T. A., Mattern, V., McGill, J. R., Harris, J. M., Sarosdy, M. F., Patel, P., and Sakaguchi, A. Y. (1997). Organization and expression of human telomere repeat binding factor genes. Somat Cell Mol Genet 23, 275-286.
[189] Yu, C. E., Oshima, J., Fu, Y. H., Wijsman, E. M., Hisama, F., Alisch, R., Matthews, S., Nakura, J., Miki, T., Ouais, S., et al. (1996). Positional cloning of the Werner's syndrome gene. Science 272, 258-262.
[190] Zakian, V. A. (1989). Structure and function of telomeres. Annu Rev Genet 23, 579-604.
[191] Zakian, V. A. (1996). Structure, function, and replication of Saccharomyces cerevisiae telomeres. Annu Rev Genet 30, 141-172.
[192] Zakian, V. A., and Pluta, A. F. (1989). Telomere formation in yeast. Nature 338, 468.
[193] Zaug, A. J., Podell, E. R., and Cech, T. R. (2005). Human POT1 disrupts telomeric G-quadruplexes allowing telomerase extension in vitro. Proc Natl Acad Sci U S A 102, 10864-10869.
[194] Zhang, D. H., Zhou, B., Huang, Y., Xu, L. X., and Zhou, J. Q. (2006). The human Pif1 helicase, a potential Escherichia coli RecD homologue, inhibits telomerase activity. Nucleic Acids Res 34, 1393-1404.
[195] Zhang P, C. S., Fu W, Mendoza M, Mattson MP. (2003). TERT suppresses apoptotis at a premitochondrial step by a mechanism requiring reverse transcriptase activity and 14-3-3 protein-binding ability. FASEB J 17, 767-769.
[196] Zhang, X., Mar, V., Zhou, W., Harrington, L., and Robinson, M. O. (1999). Telomere shortening and apoptosis in telomerase-inhibited human tumor cells. Genes Dev 13, 2388-2399.
[197] Zhou, J., Monson, E. K., Teng, S., Schulz, V. P., and Zakian, V. A. (2000). Pif1p helicase, a catalytic inhibitor of telomerase in yeast. Science 289, 771-774.
[198] Zhou, J. Q., Qi, H., Schulz, V. P., Mateyak, M. K., Monson, E. K., and Zakian, V. A. (2002). Schizosaccharomyces pombe pfh1+ encodes an essential 5' to 3' DNA helicase that is a member of the PIF1 subfamily of DNA helicases. Mol Biol Cell 13, 2180-2191.
[199] Zhou, J. Q., Tan, C. K., So, A. G., and Downey, K. M. (1996). Purification and characterization of the catalytic subunit of human DNA polymerase delta expressed in baculovirus-infected insect cells. J Biol Chem 271, 29740-29745.
[200] Zhou, X. Z., and Lu, K. P. (2001). The Pin2/TRF1-interacting protein PinX1 is a potent telomerase inhibitor. Cell 107, 347-359.
[201] Zhu, J., Wang, H., Bishop, J. M., and Blackburn, E. H. (1999). Telomerase extends the lifespan of virus-transformed human cells without net telomere lengthening. Proc Natl Acad Sci U S A 96, 3723-3728.