Skip to main content
PMC home page
Philosophical Transactions of the Royal Society B: Biological Sciences logoLink to Philosophical Transactions of the Royal Society B: Biological Sciences
. 2002 Apr 29;357(1420):545–562. doi: 10.1098/rstb.2001.1053

Tiptoeing to chromosome tips: facts, promises and perils of today's human telomere biology.

J Fajkus 1, M Simícková 1, J Maláska 1
PMCID: PMC1692969  PMID: 12028791

Abstract

The past decade has witnessed an explosion of knowledge concerning the structure and function of chromosome terminal structures-telomeres. Today's telomere research has advanced from a pure descriptive approach of DNA and protein components to an elementary understanding of telomere metabolism, and now to promising applications in medicine. These applications include 'passive' ones, among which the use of analysis of telomeres and telomerase (a cellular reverse transcriptase that synthesizes telomeres) for cancer diagnostics is the best known. The 'active' applications involve targeted downregulation or upregulation of telomere synthesis, either to mortalize immortal cancer cells, or to rejuvenate mortal somatic cells and tissues for cellular transplantations, respectively. This article reviews the basic data on structure and function of human telomeres and telomerase, as well as both passive and active applications of human telomere biology.

Full Text

The Full Text of this article is available as a PDF (461.0 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abdul-Ghani R., Ohana P., Matouk I., Ayesh S., Ayesh B., Laster M., Bibi O., Giladi H., Molnar-Kimber K., Sughayer M. A. Use of transcriptional regulatory sequences of telomerase (hTER and hTERT) for selective killing of cancer cells. Mol Ther. 2000 Dec;2(6):539–544. doi: 10.1006/mthe.2000.0196. [DOI] [PubMed] [Google Scholar]
  2. Akiyama M., Iwase S., Horiguchi-Yamada J., Saito S., Furukawa Y., Yamada O., Mizoguchi H., Ohno T., Yamada H. Interferon-alpha repressed telomerase along with G1-accumulation of Daudi cells. Cancer Lett. 1999 Jul 19;142(1):23–30. doi: 10.1016/s0304-3835(99)00109-3. [DOI] [PubMed] [Google Scholar]
  3. Albanell J., Han W., Mellado B., Gunawardane R., Scher H. I., Dmitrovsky E., Moore M. A. Telomerase activity is repressed during differentiation of maturation-sensitive but not resistant human tumor cell lines. Cancer Res. 1996 Apr 1;56(7):1503–1508. [PubMed] [Google Scholar]
  4. Arai Y., Yajima T., Yagihashi A., Kobayashi D., Kameshima H., Sasaki M., Tanaka K., Kuwajima K., Miyao N., Tsukamoto T. Limitations of urinary telomerase activity measurement in urothelial cancer. Clin Chim Acta. 2000 Jun;296(1-2):35–44. doi: 10.1016/s0009-8981(00)00202-3. [DOI] [PubMed] [Google Scholar]
  5. Arinaga M., Shimizu S., Gotoh K., Haruki N., Takahashi T., Takahashi T., Mitsudomi T. Expression of human telomerase subunit genes in primary lung cancer and its clinical significance. Ann Thorac Surg. 2000 Aug;70(2):401–406. doi: 10.1016/s0003-4975(00)01454-5. [DOI] [PubMed] [Google Scholar]
  6. Baumann P., Cech T. R. Pot1, the putative telomere end-binding protein in fission yeast and humans. Science. 2001 May 11;292(5519):1171–1175. doi: 10.1126/science.1060036. [DOI] [PubMed] [Google Scholar]
  7. Biessmann H., Mason J. M. Telomere maintenance without telomerase. Chromosoma. 1997 Jul;106(2):63–69. doi: 10.1007/s004120050225. [DOI] [PubMed] [Google Scholar]
  8. Bisoffi M., Chakerian A. E., Fore M. L., Bryant J. E., Hernandez J. P., Moyzis R. K., Griffith J. K. Inhibition of human telomerase by a retrovirus expressing telomeric antisense RNA. Eur J Cancer. 1998 Jul;34(8):1242–1249. doi: 10.1016/s0959-8049(98)00049-5. [DOI] [PubMed] [Google Scholar]
  9. Bièche I., Noguès C., Paradis V., Olivi M., Bedossa P., Lidereau R., Vidaud M. Quantitation of hTERT gene expression in sporadic breast tumors with a real-time reverse transcription-polymerase chain reaction assay. Clin Cancer Res. 2000 Feb;6(2):452–459. [PubMed] [Google Scholar]
  10. Bodnar A. G., Ouellette M., Frolkis M., Holt S. E., Chiu C. P., Morin G. B., Harley C. B., Shay J. W., Lichtsteiner S., Wright W. E. Extension of life-span by introduction of telomerase into normal human cells. Science. 1998 Jan 16;279(5349):349–352. doi: 10.1126/science.279.5349.349. [DOI] [PubMed] [Google Scholar]
  11. Broccoli D., Smogorzewska A., Chong L., de Lange T. Human telomeres contain two distinct Myb-related proteins, TRF1 and TRF2. Nat Genet. 1997 Oct;17(2):231–235. doi: 10.1038/ng1097-231. [DOI] [PubMed] [Google Scholar]
  12. Brown B. A., 2nd, Lin Y., Roberts J. F., Hardin C. C. Antibodies specific for the DNA quadruplex [d(CGC G4 GCG)4] isolated from autoimmune mice. Nucleic Acids Symp Ser. 1995;(33):134–136. [PubMed] [Google Scholar]
  13. Bryan T. M., Englezou A., Dalla-Pozza L., Dunham M. A., Reddel R. R. Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines. Nat Med. 1997 Nov;3(11):1271–1274. doi: 10.1038/nm1197-1271. [DOI] [PubMed] [Google Scholar]
  14. Bryce L. A., Morrison N., Hoare S. F., Muir S., Keith W. N. Mapping of the gene for the human telomerase reverse transcriptase, hTERT, to chromosome 5p15.33 by fluorescence in situ hybridization. Neoplasia. 2000 May-Jun;2(3):197–201. doi: 10.1038/sj.neo.7900092. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Cardenas M. E., Bianchi A., de Lange T. A Xenopus egg factor with DNA-binding properties characteristic of terminus-specific telomeric proteins. Genes Dev. 1993 May;7(5):883–894. doi: 10.1101/gad.7.5.883. [DOI] [PubMed] [Google Scholar]
  16. Carey L. A., Hedican C. A., Henderson G. S., Umbricht C. B., Dome J. S., Varon D., Sukumar S. Careful histological confirmation and microdissection reveal telomerase activity in otherwise telomerase-negative breast cancers. Clin Cancer Res. 1998 Feb;4(2):435–440. [PubMed] [Google Scholar]
  17. Chen Q., Ijpma A., Greider C. W. Two survivor pathways that allow growth in the absence of telomerase are generated by distinct telomere recombination events. Mol Cell Biol. 2001 Mar;21(5):1819–1827. doi: 10.1128/MCB.21.5.1819-1827.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Cheng C. W., Chueh S. C., Chern H. D. Diagnosis of bladder cancer using telomerase activity in voided urine. J Formos Med Assoc. 2000 Dec;99(12):920–925. [PubMed] [Google Scholar]
  19. Clark G. M., Osborne C. K., Levitt D., Wu F., Kim N. W. Telomerase activity and survival of patients with node-positive breast cancer. J Natl Cancer Inst. 1997 Dec 17;89(24):1874–1881. doi: 10.1093/jnci/89.24.1874. [DOI] [PubMed] [Google Scholar]
  20. Colgin L. M., Wilkinson C., Englezou A., Kilian A., Robinson M. O., Reddel R. R. The hTERTalpha splice variant is a dominant negative inhibitor of telomerase activity. Neoplasia. 2000 Sep-Oct;2(5):426–432. doi: 10.1038/sj.neo.7900112. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Devereux T. R., Horikawa I., Anna C. H., Annab L. A., Afshari C. A., Barrett J. C. DNA methylation analysis of the promoter region of the human telomerase reverse transcriptase (hTERT) gene. Cancer Res. 1999 Dec 15;59(24):6087–6090. [PubMed] [Google Scholar]
  22. Ebina Y., Yamada H., Fujino T., Furuta I., Sakuragi N., Yamamoto R., Katoh M., Oshimura M., Fujimoto S. Telomerase activity correlates with histo-pathological factors in uterine endometrial carcinoma. Int J Cancer. 1999 Oct 22;84(5):529–532. doi: 10.1002/(sici)1097-0215(19991022)84:5<529::aid-ijc15>3.0.co;2-j. [DOI] [PubMed] [Google Scholar]
  23. Fajkus J., Kovarík A., Královics R., Bezdek M. Organization of telomeric and subtelomeric chromatin in the higher plant Nicotiana tabacum. Mol Gen Genet. 1995 Jun 10;247(5):633–638. doi: 10.1007/BF00290355. [DOI] [PubMed] [Google Scholar]
  24. Fajkus J., Trifonov E. N. Columnar packing of telomeric nucleosomes. Biochem Biophys Res Commun. 2001 Feb 2;280(4):961–963. doi: 10.1006/bbrc.2000.4208. [DOI] [PubMed] [Google Scholar]
  25. Faraoni I., Graziani G., Turriziani M., Masci G., Mezzetti M., Testori A., Veronesi U., Bonmassar E. Suppression of telomerase activity as an indicator of drug-induced cytotoxicity against cancer cells: in vitro studies with fresh human tumor samples. Lab Invest. 1999 Aug;79(8):993–1005. [PubMed] [Google Scholar]
  26. Farwell D. G., Shera K. A., Koop J. I., Bonnet G. A., Matthews C. P., Reuther G. W., Coltrera M. D., McDougall J. K., Klingelhutz A. J. Genetic and epigenetic changes in human epithelial cells immortalized by telomerase. Am J Pathol. 2000 May;156(5):1537–1547. doi: 10.1016/S0002-9440(10)65025-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Feng J., Funk W. D., Wang S. S., Weinrich S. L., Avilion A. A., Chiu C. P., Adams R. R., Chang E., Allsopp R. C., Yu J. The RNA component of human telomerase. Science. 1995 Sep 1;269(5228):1236–1241. doi: 10.1126/science.7544491. [DOI] [PubMed] [Google Scholar]
  28. Ferlicot S., Paradis V., Dargère D., Monges G., Bedossa P. Detection of telomerase in hepatocellular carcinomas using a PCR ELISA assay: comparison with hTR expression. J Clin Pathol. 1999 Oct;52(10):725–729. doi: 10.1136/jcp.52.10.725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Folini M., Colella G., Villa R., Lualdi S., Daidone M. G., Zaffaroni N. Inhibition of telomerase activity by a hammerhead ribozyme targeting the RNA component of telomerase in human melanoma cells. J Invest Dermatol. 2000 Feb;114(2):259–267. doi: 10.1046/j.1523-1747.2000.00870.x. [DOI] [PubMed] [Google Scholar]
  30. Folini M., De Marco C., Orlandi L., Daidone M. G., Zaffaroni N. Attenuation of telomerase activity does not increase sensitivity of human melanoma cells to anticancer agents. Eur J Cancer. 2000 Oct;36(16):2137–2145. doi: 10.1016/s0959-8049(00)00295-1. [DOI] [PubMed] [Google Scholar]
  31. Fossel M. Telomerase and the aging cell: implications for human health. JAMA. 1998 Jun 3;279(21):1732–1735. doi: 10.1001/jama.279.21.1732. [DOI] [PubMed] [Google Scholar]
  32. Fujimoto K., Kyo S., Takakura M., Kanaya T., Kitagawa Y., Itoh H., Takahashi M., Inoue M. Identification and characterization of negative regulatory elements of the human telomerase catalytic subunit (hTERT) gene promoter: possible role of MZF-2 in transcriptional repression of hTERT. Nucleic Acids Res. 2000 Jul 1;28(13):2557–2562. doi: 10.1093/nar/28.13.2557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Fujioka T., Hasegawa M., Suzuki Y., Suzuki T., Sugimura J., Tanji S., Koike H. Telomerase activity in human renal cell carcinoma. Int J Urol. 2000 Jan;7(1):16–21. doi: 10.1046/j.1442-2042.2000.00130.x. [DOI] [PubMed] [Google Scholar]
  34. Fuxe J., Akusjärvi G., Goike H. M., Roos G., Collins V. P., Pettersson R. F. Adenovirus-mediated overexpression of p15INK4B inhibits human glioma cell growth, induces replicative senescence, and inhibits telomerase activity similarly to p16INK4A. Cell Growth Differ. 2000 Jul;11(7):373–384. [PubMed] [Google Scholar]
  35. Glukhov A. I., Zimnik O. V., Gordeev S. A., Severin S. E. Inhibition of telomerase activity of melanoma cells in vitro by antisense oligonucleotides. Biochem Biophys Res Commun. 1998 Jul 20;248(2):368–371. doi: 10.1006/bbrc.1998.8801. [DOI] [PubMed] [Google Scholar]
  36. Gomez D. E., Tejera A. M., Olivero O. A. Irreversible telomere shortening by 3'-azido-2',3'-dideoxythymidine (AZT) treatment. Biochem Biophys Res Commun. 1998 May 8;246(1):107–110. doi: 10.1006/bbrc.1998.8555. [DOI] [PubMed] [Google Scholar]
  37. Greider C. W., Blackburn E. H. Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell. 1985 Dec;43(2 Pt 1):405–413. doi: 10.1016/0092-8674(85)90170-9. [DOI] [PubMed] [Google Scholar]
  38. Greider C. W. Telomerase activity, cell proliferation, and cancer. Proc Natl Acad Sci U S A. 1998 Jan 6;95(1):90–92. doi: 10.1073/pnas.95.1.90. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Griffith J. D., Comeau L., Rosenfield S., Stansel R. M., Bianchi A., Moss H., de Lange T. Mammalian telomeres end in a large duplex loop. Cell. 1999 May 14;97(4):503–514. doi: 10.1016/s0092-8674(00)80760-6. [DOI] [PubMed] [Google Scholar]
  40. Gu J., Kagawa S., Takakura M., Kyo S., Inoue M., Roth J. A., Fang B. Tumor-specific transgene expression from the human telomerase reverse transcriptase promoter enables targeting of the therapeutic effects of the Bax gene to cancers. Cancer Res. 2000 Oct 1;60(19):5359–5364. [PubMed] [Google Scholar]
  41. Guiducci C., Cerone M. A., Bacchetti S. Expression of mutant telomerase in immortal telomerase-negative human cells results in cell cycle deregulation, nuclear and chromosomal abnormalities and rapid loss of viability. Oncogene. 2001 Feb 8;20(6):714–725. doi: 10.1038/sj.onc.1204145. [DOI] [PubMed] [Google Scholar]
  42. Hahn W. C., Stewart S. A., Brooks M. W., York S. G., Eaton E., Kurachi A., Beijersbergen R. L., Knoll J. H., Meyerson M., Weinberg R. A. Inhibition of telomerase limits the growth of human cancer cells. Nat Med. 1999 Oct;5(10):1164–1170. doi: 10.1038/13495. [DOI] [PubMed] [Google Scholar]
  43. Hamilton S. E., Simmons C. G., Kathiriya I. S., Corey D. R. Cellular delivery of peptide nucleic acids and inhibition of human telomerase. Chem Biol. 1999 Jun;6(6):343–351. doi: 10.1016/S1074-5521(99)80046-5. [DOI] [PubMed] [Google Scholar]
  44. Harrison R. J., Gowan S. M., Kelland L. R., Neidle S. Human telomerase inhibition by substituted acridine derivatives. Bioorg Med Chem Lett. 1999 Sep 6;9(17):2463–2468. doi: 10.1016/s0960-894x(99)00394-7. [DOI] [PubMed] [Google Scholar]
  45. Haïk S., Gauthier L. R., Granotier C., Peyrin J. M., Lages C. S., Dormont D., Boussin F. D. Fibroblast growth factor 2 up regulates telomerase activity in neural precursor cells. Oncogene. 2000 Jun 15;19(26):2957–2966. doi: 10.1038/sj.onc.1203596. [DOI] [PubMed] [Google Scholar]
  46. Henriksson M., Lüscher B. Proteins of the Myc network: essential regulators of cell growth and differentiation. Adv Cancer Res. 1996;68:109–182. doi: 10.1016/s0065-230x(08)60353-x. [DOI] [PubMed] [Google Scholar]
  47. Herbert B. S., Wright W. E., Shay J. W. Telomerase and breast cancer. Breast Cancer Res. 2001 Feb 22;3(3):146–149. doi: 10.1186/bcr288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Hoare S. F., Bryce L. A., Wisman G. B., Burns S., Going J. J., van der Zee A. G., Keith W. N. Lack of telomerase RNA gene hTERC expression in alternative lengthening of telomeres cells is associated with methylation of the hTERC promoter. Cancer Res. 2001 Jan 1;61(1):27–32. [PubMed] [Google Scholar]
  49. Holt S. E., Aisner D. L., Baur J., Tesmer V. M., Dy M., Ouellette M., Trager J. B., Morin G. B., Toft D. O., Shay J. W. Functional requirement of p23 and Hsp90 in telomerase complexes. Genes Dev. 1999 Apr 1;13(7):817–826. doi: 10.1101/gad.13.7.817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Holt S. E., Shay J. W., Wright W. E. Refining the telomere-telomerase hypothesis of aging and cancer. Nat Biotechnol. 1996 Jul;14(7):836–839. doi: 10.1038/nbt0796-836. [DOI] [PubMed] [Google Scholar]
  51. Horikawa I., Oshimura M., Barrett J. C. Repression of the telomerase catalytic subunit by a gene on human chromosome 3 that induces cellular senescence. Mol Carcinog. 1998 Jun;22(2):65–72. doi: 10.1002/(sici)1098-2744(199806)22:2<65::aid-mc1>3.0.co;2-j. [DOI] [PubMed] [Google Scholar]
  52. Hsu H. L., Gilley D., Galande S. A., Hande M. P., Allen B., Kim S. H., Li G. C., Campisi J., Kohwi-Shigematsu T., Chen D. J. Ku acts in a unique way at the mammalian telomere to prevent end joining. Genes Dev. 2000 Nov 15;14(22):2807–2812. doi: 10.1101/gad.844000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Huang P., Pryde F. E., Lester D., Maddison R. L., Borts R. H., Hickson I. D., Louis E. J. SGS1 is required for telomere elongation in the absence of telomerase. Curr Biol. 2001 Jan 23;11(2):125–129. doi: 10.1016/s0960-9822(01)00021-5. [DOI] [PubMed] [Google Scholar]
  54. Izbicka E., Wheelhouse R. T., Raymond E., Davidson K. K., Lawrence R. A., Sun D., Windle B. E., Hurley L. H., Von Hoff D. D. Effects of cationic porphyrins as G-quadruplex interactive agents in human tumor cells. Cancer Res. 1999 Feb 1;59(3):639–644. [PubMed] [Google Scholar]
  55. Jiang X. R., Jimenez G., Chang E., Frolkis M., Kusler B., Sage M., Beeche M., Bodnar A. G., Wahl G. M., Tlsty T. D. Telomerase expression in human somatic cells does not induce changes associated with a transformed phenotype. Nat Genet. 1999 Jan;21(1):111–114. doi: 10.1038/5056. [DOI] [PubMed] [Google Scholar]
  56. Kakeji Y., Maehara Y., Koga T., Shibahara K., Kabashima A., Tokunaga E., Sugimachi K. Gastric cancer with high telomerase activity shows rapid development and invasiveness. Oncol Rep. 2001 Jan-Feb;8(1):107–110. [PubMed] [Google Scholar]
  57. Kanaya T., Kyo S., Hamada K., Takakura M., Kitagawa Y., Harada H., Inoue M. Adenoviral expression of p53 represses telomerase activity through down-regulation of human telomerase reverse transcriptase transcription. Clin Cancer Res. 2000 Apr;6(4):1239–1247. [PubMed] [Google Scholar]
  58. Kanazawa Y., Ohkawa K., Ueda K., Mita E., Takehara T., Sasaki Y., Kasahara A., Hayashi N. Hammerhead ribozyme-mediated inhibition of telomerase activity in extracts of human hepatocellular carcinoma cells. Biochem Biophys Res Commun. 1996 Aug 14;225(2):570–576. doi: 10.1006/bbrc.1996.1213. [DOI] [PubMed] [Google Scholar]
  59. Kerwin S. M. G-Quadruplex DNA as a target for drug design. Curr Pharm Des. 2000 Mar;6(4):441–478. doi: 10.2174/1381612003400849. [DOI] [PubMed] [Google Scholar]
  60. Kharbanda S., Kumar V., Dhar S., Pandey P., Chen C., Majumder P., Yuan Z. M., Whang Y., Strauss W., Pandita T. K. Regulation of the hTERT telomerase catalytic subunit by the c-Abl tyrosine kinase. Curr Biol. 2000 May 18;10(10):568–575. doi: 10.1016/s0960-9822(00)00483-8. [DOI] [PubMed] [Google Scholar]
  61. Kickhoefer V. A., Liu Y., Kong L. B., Snow B. E., Stewart P. L., Harrington L., Rome L. H. The Telomerase/vault-associated protein TEP1 is required for vault RNA stability and its association with the vault particle. J Cell Biol. 2001 Jan 8;152(1):157–164. doi: 10.1083/jcb.152.1.157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. 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., Shay J. W. Specific association of human telomerase activity with immortal cells and cancer. Science. 1994 Dec 23;266(5193):2011–2015. doi: 10.1126/science.7605428. [DOI] [PubMed] [Google Scholar]
  63. Kim S. H., Kaminker P., Campisi J. TIN2, a new regulator of telomere length in human cells. Nat Genet. 1999 Dec;23(4):405–412. doi: 10.1038/70508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Koeneman K. S., Pan C. X., Jin J. K., Pyle J. M., 3rd, Flanigan R. C., Shankey T. V., Diaz M. O. Telomerase activity, telomere length, and DNA ploidy in prostatic intraepithelial neoplasia (PIN). J Urol. 1998 Oct;160(4):1533–1539. [PubMed] [Google Scholar]
  65. Koga S., Hirohata S., Kondo Y., Komata T., Takakura M., Inoue M., Kyo S., Kondo S. A novel telomerase-specific gene therapy: gene transfer of caspase-8 utilizing the human telomerase catalytic subunit gene promoter. Hum Gene Ther. 2000 Jul 1;11(10):1397–1406. doi: 10.1089/10430340050057477. [DOI] [PubMed] [Google Scholar]
  66. Komata T., Kondo Y., Kanzawa T., Hirohata S., Koga S., Sumiyoshi H., Srinivasula S. M., Barna B. P., Germano I. M., Takakura M. Treatment of malignant glioma cells with the transfer of constitutively active caspase-6 using the human telomerase catalytic subunit (human telomerase reverse transcriptase) gene promoter. Cancer Res. 2001 Aug 1;61(15):5796–5802. [PubMed] [Google Scholar]
  67. Kondo S., Kondo Y., Li G., Silverman R. H., Cowell J. K. Targeted therapy of human malignant glioma in a mouse model by 2-5A antisense directed against telomerase RNA. Oncogene. 1998 Jun 25;16(25):3323–3330. doi: 10.1038/sj.onc.1201885. [DOI] [PubMed] [Google Scholar]
  68. Kondo S., Tanaka Y., Kondo Y., Hitomi M., Barnett G. H., Ishizaka Y., Liu J., Haqqi T., Nishiyama A., Villeponteau B. Antisense telomerase treatment: induction of two distinct pathways, apoptosis and differentiation. FASEB J. 1998 Jul;12(10):801–811. doi: 10.1096/fasebj.12.10.801. [DOI] [PubMed] [Google Scholar]
  69. Kondo Y., Koga S., Komata T., Kondo S. Treatment of prostate cancer in vitro and in vivo with 2-5A-anti-telomerase RNA component. Oncogene. 2000 Apr 27;19(18):2205–2211. doi: 10.1038/sj.onc.1203538. [DOI] [PubMed] [Google Scholar]
  70. Kondo Y., Kondo S., Tanaka Y., Haqqi T., Barna B. P., Cowell J. K. Inhibition of telomerase increases the susceptibility of human malignant glioblastoma cells to cisplatin-induced apoptosis. Oncogene. 1998 Apr 30;16(17):2243–2248. doi: 10.1038/sj.onc.1201754. [DOI] [PubMed] [Google Scholar]
  71. Koscielny S., Fiedler W., Dahse R., Beleites E. Reaktivierung der Telomerase in Plattenepithelkarzinomen des Kopf-Hals-Bereiches. Laryngorhinootologie. 2000 Sep;79(9):551–556. doi: 10.1055/s-2000-6937. [DOI] [PubMed] [Google Scholar]
  72. Kumaki F., Kawai T., Hiroi S., Shinomiya N., Ozeki Y., Ferrans V. J., Torikata C. Telomerase activity and expression of human telomerase RNA component and human telomerase reverse transcriptase in lung carcinomas. Hum Pathol. 2001 Feb;32(2):188–195. doi: 10.1053/hupa.2001.21567. [DOI] [PubMed] [Google Scholar]
  73. Kushner D. M., Paranjape J. M., Bandyopadhyay B., Cramer H., Leaman D. W., Kennedy A. W., Silverman R. H., Cowell J. K. 2-5A antisense directed against telomerase RNA produces apoptosis in ovarian cancer cells. Gynecol Oncol. 2000 Feb;76(2):183–192. doi: 10.1006/gyno.1999.5668. [DOI] [PubMed] [Google Scholar]
  74. Kyo S., Takakura M., Kanaya T., Zhuo W., Fujimoto K., Nishio Y., Orimo A., Inoue M. Estrogen activates telomerase. Cancer Res. 1999 Dec 1;59(23):5917–5921. [PubMed] [Google Scholar]
  75. Kyo S., Takakura M., Taira T., Kanaya T., Itoh H., Yutsudo M., Ariga H., Inoue M. Sp1 cooperates with c-Myc to activate transcription of the human telomerase reverse transcriptase gene (hTERT). Nucleic Acids Res. 2000 Feb 1;28(3):669–677. doi: 10.1093/nar/28.3.669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. Laroche T., Martin S. G., Gotta M., Gorham H. C., Pryde F. E., Louis E. J., Gasser S. M. Mutation of yeast Ku genes disrupts the subnuclear organization of telomeres. Curr Biol. 1998 May 21;8(11):653–656. doi: 10.1016/s0960-9822(98)70252-0. [DOI] [PubMed] [Google Scholar]
  77. Le S., Moore J. K., Haber J. E., Greider C. W. RAD50 and RAD51 define two pathways that collaborate to maintain telomeres in the absence of telomerase. Genetics. 1999 May;152(1):143–152. doi: 10.1093/genetics/152.1.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Lingner J., Cech T. R. Telomerase and chromosome end maintenance. Curr Opin Genet Dev. 1998 Apr;8(2):226–232. doi: 10.1016/s0959-437x(98)80145-7. [DOI] [PubMed] [Google Scholar]
  79. Makarov V. L., Lejnine S., Bedoyan J., Langmore J. P. Nucleosomal organization of telomere-specific chromatin in rat. Cell. 1993 May 21;73(4):775–787. doi: 10.1016/0092-8674(93)90256-p. [DOI] [PubMed] [Google Scholar]
  80. Mata J. E., Joshi S. S., Palen B., Pirruccello S. J., Jackson J. D., Elias N., Page T. J., Medlin K. L., Iversen P. L. A hexameric phosphorothioate oligonucleotide telomerase inhibitor arrests growth of Burkitt's lymphoma cells in vitro and in vivo. Toxicol Appl Pharmacol. 1997 May;144(1):189–197. doi: 10.1006/taap.1997.8103. [DOI] [PubMed] [Google Scholar]
  81. Mehle C., Piatyszek M. A., Ljungberg B., Shay J. W., Roos G. Telomerase activity in human renal cell carcinoma. Oncogene. 1996 Jul 4;13(1):161–166. [PubMed] [Google Scholar]
  82. Mergny J. L., Mailliet P., Lavelle F., Riou J. F., Laoui A., Hélène C. The development of telomerase inhibitors: the G-quartet approach. Anticancer Drug Des. 1999 Aug;14(4):327–339. [PubMed] [Google Scholar]
  83. Meyerson M., Counter C. M., Eaton E. N., Ellisen L. W., Steiner P., Caddle S. D., Ziaugra L., Beijersbergen R. L., Davidoff M. J., Liu Q. hEST2, the putative human telomerase catalytic subunit gene, is up-regulated in tumor cells and during immortalization. Cell. 1997 Aug 22;90(4):785–795. doi: 10.1016/s0092-8674(00)80538-3. [DOI] [PubMed] [Google Scholar]
  84. Minev B., Hipp J., Firat H., Schmidt J. D., Langlade-Demoyen P., Zanetti M. Cytotoxic T cell immunity against telomerase reverse transcriptase in humans. Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4796–4801. doi: 10.1073/pnas.070560797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  85. Misiti S., Nanni S., Fontemaggi G., Cong Y. S., Wen J., Hirte H. W., Piaggio G., Sacchi A., Pontecorvi A., Bacchetti S. Induction of hTERT expression and telomerase activity by estrogens in human ovary epithelium cells. Mol Cell Biol. 2000 Jun;20(11):3764–3771. doi: 10.1128/mcb.20.11.3764-3771.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  86. Mitchell J. R., Wood E., Collins K. A telomerase component is defective in the human disease dyskeratosis congenita. Nature. 1999 Dec 2;402(6761):551–555. doi: 10.1038/990141. [DOI] [PubMed] [Google Scholar]
  87. Morales C. P., Burdick J. S., Saboorian M. H., Wright W. E., Shay J. W. In situ hybridization for telomerase RNA in routine cytologic brushings for the diagnosis of pancreaticobiliary malignancies. Gastrointest Endosc. 1998 Oct;48(4):402–405. doi: 10.1016/s0016-5107(98)70011-2. [DOI] [PubMed] [Google Scholar]
  88. Morales C. P., Holt S. E., Ouellette M., Kaur K. J., Yan Y., Wilson K. S., White M. A., Wright W. E., Shay J. W. Absence of cancer-associated changes in human fibroblasts immortalized with telomerase. Nat Genet. 1999 Jan;21(1):115–118. doi: 10.1038/5063. [DOI] [PubMed] [Google Scholar]
  89. Muniyappa K., Anuradha S., Byers B. Yeast meiosis-specific protein Hop1 binds to G4 DNA and promotes its formation. Mol Cell Biol. 2000 Feb;20(4):1361–1369. doi: 10.1128/mcb.20.4.1361-1369.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  90. Murakami J., Nagai N., Ohama K. Telomerase activity in body cavity fluid and peritoneal washings in uterine and ovarian cancer. J Int Med Res. 1998 Jun-Jul;26(3):129–139. doi: 10.1177/030006059802600303. [DOI] [PubMed] [Google Scholar]
  91. Naasani I., Seimiya H., Tsuruo T. Telomerase inhibition, telomere shortening, and senescence of cancer cells by tea catechins. Biochem Biophys Res Commun. 1998 Aug 19;249(2):391–396. doi: 10.1006/bbrc.1998.9075. [DOI] [PubMed] [Google Scholar]
  92. Naasani I., Seimiya H., Yamori T., Tsuruo T. FJ5002: a potent telomerase inhibitor identified by exploiting the disease-oriented screening program with COMPARE analysis. Cancer Res. 1999 Aug 15;59(16):4004–4011. [PubMed] [Google Scholar]
  93. Naka K., Yokozaki H., Yasui W., Tahara H., Tahara E., Tahara E. Effect of antisense human telomerase RNA transfection on the growth of human gastric cancer cell lines. Biochem Biophys Res Commun. 1999 Feb 24;255(3):753–758. doi: 10.1006/bbrc.1998.9938. [DOI] [PubMed] [Google Scholar]
  94. Nakabayashi K., Ogino H., Michishita E., Satoh N., Ayusawa D. Introduction of chromosome 7 suppresses telomerase with shortening of telomeres in a human mesothelial cell line. Exp Cell Res. 1999 Nov 1;252(2):376–382. doi: 10.1006/excr.1999.4619. [DOI] [PubMed] [Google Scholar]
  95. Neidle S., Kelland L. R. Telomerase as an anti-cancer target: current status and future prospects. Anticancer Drug Des. 1999 Aug;14(4):341–347. [PubMed] [Google Scholar]
  96. Nishimoto A., Miura N., Horikawa I., Kugoh H., Murakami Y., Hirohashi S., Kawasaki H., Gazdar A. F., Shay J. W., Barrett J. C. Functional evidence for a telomerase repressor gene on human chromosome 10p15.1. Oncogene. 2001 Feb 15;20(7):828–835. doi: 10.1038/sj.onc.1204165. [DOI] [PubMed] [Google Scholar]
  97. Norton J. C., Piatyszek M. A., Wright W. E., Shay J. W., Corey D. R. Inhibition of human telomerase activity by peptide nucleic acids. Nat Biotechnol. 1996 May;14(5):615–619. doi: 10.1038/nbt0596-615. [DOI] [PubMed] [Google Scholar]
  98. O'Hare M. J., Bond J., Clarke C., Takeuchi Y., Atherton A. J., Berry C., Moody J., Silver A. R., Davies D. C., Alsop A. E. Conditional immortalization of freshly isolated human mammary fibroblasts and endothelial cells. Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):646–651. doi: 10.1073/pnas.98.2.646. [DOI] [PMC free article] [PubMed] [Google Scholar]
  99. Oh S., Song Y. H., Yim J., Kim T. K. Identification of Mad as a repressor of the human telomerase (hTERT) gene. Oncogene. 2000 Mar 9;19(11):1485–1490. doi: 10.1038/sj.onc.1203439. [DOI] [PubMed] [Google Scholar]
  100. Ohnuma T., Li F. L., Holland J. F. Inhibitory effects of telomere-mimic phosphorothioate oligonucleotides on various human tumor cells in vitro. Anticancer Res. 1997 Jul-Aug;17(4A):2455–2458. [PubMed] [Google Scholar]
  101. Olovnikov A. M. A theory of marginotomy. The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon. J Theor Biol. 1973 Sep 14;41(1):181–190. doi: 10.1016/0022-5193(73)90198-7. [DOI] [PubMed] [Google Scholar]
  102. Ouellette M. M., McDaniel L. D., Wright W. E., Shay J. W., Schultz R. A. The establishment of telomerase-immortalized cell lines representing human chromosome instability syndromes. Hum Mol Genet. 2000 Feb 12;9(3):403–411. doi: 10.1093/hmg/9.3.403. [DOI] [PubMed] [Google Scholar]
  103. Park T. W., Riethdorf S., Riethdorf L., Löning T., Jänicke F. Differential telomerase activity, expression of the telomerase catalytic sub-unit and telomerase-RNA in ovarian tumors. Int J Cancer. 1999 Aug 20;84(4):426–431. doi: 10.1002/(sici)1097-0215(19990820)84:4<426::aid-ijc17>3.0.co;2-1. [DOI] [PubMed] [Google Scholar]
  104. Perrem K., Bryan T. M., Englezou A., Hackl T., Moy E. L., Reddel R. R. Repression of an alternative mechanism for lengthening of telomeres in somatic cell hybrids. Oncogene. 1999 Jun 3;18(22):3383–3390. doi: 10.1038/sj.onc.1202752. [DOI] [PubMed] [Google Scholar]
  105. Perrem K., Colgin L. M., Neumann A. A., Yeager T. R., Reddel R. R. Coexistence of alternative lengthening of telomeres and telomerase in hTERT-transfected GM847 cells. Mol Cell Biol. 2001 Jun;21(12):3862–3875. doi: 10.1128/MCB.21.12.3862-3875.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  106. Perry P. J., Gowan S. M., Reszka A. P., Polucci P., Jenkins T. C., Kelland L. R., Neidle S. 1,4- and 2,6-disubstituted amidoanthracene-9,10-dione derivatives as inhibitors of human telomerase. J Med Chem. 1998 Aug 13;41(17):3253–3260. doi: 10.1021/jm9801105. [DOI] [PubMed] [Google Scholar]
  107. Perry P. J., Read M. A., Davies R. T., Gowan S. M., Reszka A. P., Wood A. A., Kelland L. R., Neidle S. 2,7-Disubstituted amidofluorenone derivatives as inhibitors of human telomerase. J Med Chem. 1999 Jul 15;42(14):2679–2684. doi: 10.1021/jm990084q. [DOI] [PubMed] [Google Scholar]
  108. Perry P. J., Reszka A. P., Wood A. A., Read M. A., Gowan S. M., Dosanjh H. S., Trent J. O., Jenkins T. C., Kelland L. R., Neidle S. Human telomerase inhibition by regioisomeric disubstituted amidoanthracene-9,10-diones. J Med Chem. 1998 Nov 19;41(24):4873–4884. doi: 10.1021/jm981067o. [DOI] [PubMed] [Google Scholar]
  109. Perry PJ, Jenkins TC. Recent advances in the development of telomerase inhibitors for the treatment of cancer. Expert Opin Investig Drugs. 1999 Dec;8(12):1981–2008. doi: 10.1517/13543784.8.12.1981. [DOI] [PubMed] [Google Scholar]
  110. Price C. M., Cech T. R. Properties of the telomeric DNA-binding protein from Oxytricha nova. Biochemistry. 1989 Jan 24;28(2):769–774. doi: 10.1021/bi00428a053. [DOI] [PubMed] [Google Scholar]
  111. Price C. M. Telomere structure in Euplotes crassus: characterization of DNA-protein interactions and isolation of a telomere-binding protein. Mol Cell Biol. 1990 Jul;10(7):3421–3431. doi: 10.1128/mcb.10.7.3421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  112. Ramirez R. D., D'Atri S., Pagani E., Faraggiana T., Lacal P. M., Taylor R. S., Shay J. W. Progressive increase in telomerase activity from benign melanocytic conditions to malignant melanoma. Neoplasia. 1999 Apr;1(1):42–49. doi: 10.1038/sj.neo.7900004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  113. Ray A., Nordén B. Peptide nucleic acid (PNA): its medical and biotechnical applications and promise for the future. FASEB J. 2000 Jun;14(9):1041–1060. doi: 10.1096/fasebj.14.9.1041. [DOI] [PubMed] [Google Scholar]
  114. Raymond E., Soria J. C., Izbicka E., Boussin F., Hurley L., Von Hoff D. D. DNA G-quadruplexes, telomere-specific proteins and telomere-associated enzymes as potential targets for new anticancer drugs. Invest New Drugs. 2000 May;18(2):123–137. doi: 10.1023/a:1006373812586. [DOI] [PubMed] [Google Scholar]
  115. Reddel R. R., Bryan T. M., Murnane J. P. Immortalized cells with no detectable telomerase activity. A review. Biochemistry (Mosc) 1997 Nov;62(11):1254–1262. [PubMed] [Google Scholar]
  116. Riethman H. C., Xiang Z., Paul S., Morse E., Hu X. L., Flint J., Chi H. C., Grady D. L., Moyzis R. K. Integration of telomere sequences with the draft human genome sequence. Nature. 2001 Feb 15;409(6822):948–951. doi: 10.1038/35057180. [DOI] [PubMed] [Google Scholar]
  117. Riha K., McKnight T. D., Fajkus J., Vyskot B., Shippen D. E. Analysis of the G-overhang structures on plant telomeres: evidence for two distinct telomere architectures. Plant J. 2000 Sep;23(5):633–641. doi: 10.1046/j.1365-313x.2000.00831.x. [DOI] [PubMed] [Google Scholar]
  118. Rossetti L., Cacchione S., Fuà M., Savino M. Nucleosome assembly on telomeric sequences. Biochemistry. 1998 May 12;37(19):6727–6737. doi: 10.1021/bi9726180. [DOI] [PubMed] [Google Scholar]
  119. Rudolph P., Schubert C., Tamm S., Heidorn K., Hauschild A., Michalska I., Majewski S., Krupp G., Jablonska S., Parwaresch R. Telomerase activity in melanocytic lesions: A potential marker of tumor biology. Am J Pathol. 2000 Apr;156(4):1425–1432. doi: 10.1016/S0002-9440(10)65011-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  120. Sakamoto M., Toyoizumi T., Kikuchi Y., Okamoto A., Nakayama H., Aoki D., Yamamoto K., Hata H., Sugishita T., Tenjin Y. Telomerase activity in gynecological tumors. Oncol Rep. 2000 Sep-Oct;7(5):1003–1009. doi: 10.3892/or.7.5.1003. [DOI] [PubMed] [Google Scholar]
  121. Samper E., Goytisolo F. A., Slijepcevic P., van Buul P. P., Blasco M. A. Mammalian Ku86 protein prevents telomeric fusions independently of the length of TTAGGG repeats and the G-strand overhang. EMBO Rep. 2000 Sep;1(3):244–252. doi: 10.1093/embo-reports/kvd051. [DOI] [PMC free article] [PubMed] [Google Scholar]
  122. Saretzki G., Sitte N., Merkel U., Wurm R. E., von Zglinicki T. Telomere shortening triggers a p53-dependent cell cycle arrest via accumulation of G-rich single stranded DNA fragments. Oncogene. 1999 Sep 16;18(37):5148–5158. doi: 10.1038/sj.onc.1202898. [DOI] [PubMed] [Google Scholar]
  123. Shammas M. A., Simmons C. G., Corey D. R., Shmookler Reis R. J. Telomerase inhibition by peptide nucleic acids reverses 'immortality' of transformed human cells. Oncogene. 1999 Nov 4;18(46):6191–6200. doi: 10.1038/sj.onc.1203069. [DOI] [PubMed] [Google Scholar]
  124. Shay J. W., Bacchetti S. A survey of telomerase activity in human cancer. Eur J Cancer. 1997 Apr;33(5):787–791. doi: 10.1016/S0959-8049(97)00062-2. [DOI] [PubMed] [Google Scholar]
  125. Shay J. W., Wright W. E. Telomeres and telomerase: implications for cancer and aging. Radiat Res. 2001 Jan;155(1 Pt 2):188–193. doi: 10.1667/0033-7587(2001)155[0188:tatifc]2.0.co;2. [DOI] [PubMed] [Google Scholar]
  126. Shay J. W., Zou Y., Hiyama E., Wright W. E. Telomerase and cancer. Hum Mol Genet. 2001 Apr;10(7):677–685. doi: 10.1093/hmg/10.7.677. [DOI] [PubMed] [Google Scholar]
  127. Simícková M., Nekulová M., Pecen L., Cernoch M., Vagundová M., Pacovský Z. Quantitative determination of telomerase activity in breast cancer and benign breast diseases. Neoplasma. 2001;48(4):267–273. [PubMed] [Google Scholar]
  128. Smith S., Giriat I., Schmitt A., de Lange T. Tankyrase, a poly(ADP-ribose) polymerase at human telomeres. Science. 1998 Nov 20;282(5393):1484–1487. doi: 10.1126/science.282.5393.1484. [DOI] [PubMed] [Google Scholar]
  129. Smith S., de Lange T. Tankyrase promotes telomere elongation in human cells. Curr Biol. 2000 Oct 19;10(20):1299–1302. doi: 10.1016/s0960-9822(00)00752-1. [DOI] [PubMed] [Google Scholar]
  130. Smogorzewska A., van Steensel B., Bianchi A., Oelmann S., Schaefer M. R., Schnapp G., de Lange T. Control of human telomere length by TRF1 and TRF2. Mol Cell Biol. 2000 Mar;20(5):1659–1668. doi: 10.1128/mcb.20.5.1659-1668.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  131. Soder A. I., Hoare S. F., Muir S., Going J. J., Parkinson E. K., Keith W. N. Amplification, increased dosage and in situ expression of the telomerase RNA gene in human cancer. Oncogene. 1997 Mar 6;14(9):1013–1021. doi: 10.1038/sj.onc.1201066. [DOI] [PubMed] [Google Scholar]
  132. Song K., Jung D., Jung Y., Lee S. G., Lee I. Interaction of human Ku70 with TRF2. FEBS Lett. 2000 Sep 8;481(1):81–85. doi: 10.1016/s0014-5793(00)01958-x. [DOI] [PubMed] [Google Scholar]
  133. Soria J. C., Gauthier L. R., Raymond E., Granotier C., Morat L., Armand J. P., Boussin F. D., Sabatier L. Molecular detection of telomerase-positive circulating epithelial cells in metastatic breast cancer patients. Clin Cancer Res. 1999 May;5(5):971–975. [PubMed] [Google Scholar]
  134. Steinert S., Shay J. W., Wright W. E. Transient expression of human telomerase extends the life span of normal human fibroblasts. Biochem Biophys Res Commun. 2000 Jul 14;273(3):1095–1098. doi: 10.1006/bbrc.2000.3080. [DOI] [PubMed] [Google Scholar]
  135. Strahl C., Blackburn E. H. Effects of reverse transcriptase inhibitors on telomere length and telomerase activity in two immortalized human cell lines. Mol Cell Biol. 1996 Jan;16(1):53–65. doi: 10.1128/mcb.16.1.53. [DOI] [PMC free article] [PubMed] [Google Scholar]
  136. Tabata Y., Ikegami S., Yaguchi T., Sasaki T., Hoshiko S., Sakuma S., Shin-Ya K., Seto H. Diazaphilonic acid, a new azaphilone with telomerase inhibitory activity. J Antibiot (Tokyo) 1999 Apr;52(4):412–414. doi: 10.7164/antibiotics.52.412. [DOI] [PubMed] [Google Scholar]
  137. Tahara H., Yasui W., Tahara E., Fujimoto J., Ito K., Tamai K., Nakayama J., Ishikawa F., Tahara E., Ide T. Immuno-histochemical detection of human telomerase catalytic component, hTERT, in human colorectal tumor and non-tumor tissue sections. Oncogene. 1999 Feb 25;18(8):1561–1567. doi: 10.1038/sj.onc.1202458. [DOI] [PubMed] [Google Scholar]
  138. Tanaka H., Shimizu M., Horikawa I., Kugoh H., Yokota J., Barrett J. C., Oshimura M. Evidence for a putative telomerase repressor gene in the 3p14.2-p21.1 region. Genes Chromosomes Cancer. 1998 Oct;23(2):123–133. doi: 10.1002/(sici)1098-2264(199810)23:2<123::aid-gcc5>3.0.co;2-4. [DOI] [PubMed] [Google Scholar]
  139. Tatsumoto N., Hiyama E., Murakami Y., Imamura Y., Shay J. W., Matsuura Y., Yokoyama T. High telomerase activity is an independent prognostic indicator of poor outcome in colorectal cancer. Clin Cancer Res. 2000 Jul;6(7):2696–2701. [PubMed] [Google Scholar]
  140. Thomas M., Yang L., Hornsby P. J. Formation of functional tissue from transplanted adrenocortical cells expressing telomerase reverse transcriptase. Nat Biotechnol. 2000 Jan;18(1):39–42. doi: 10.1038/71894. [DOI] [PubMed] [Google Scholar]
  141. Tommerup H., Dousmanis A., de Lange T. Unusual chromatin in human telomeres. Mol Cell Biol. 1994 Sep;14(9):5777–5785. doi: 10.1128/mcb.14.9.5777. [DOI] [PMC free article] [PubMed] [Google Scholar]
  142. Ulaner G. A., Hu J. F., Vu T. H., Giudice L. C., Hoffman A. R. Telomerase activity in human development is regulated by human telomerase reverse transcriptase (hTERT) transcription and by alternate splicing of hTERT transcripts. Cancer Res. 1998 Sep 15;58(18):4168–4172. [PubMed] [Google Scholar]
  143. Veldman T., Horikawa I., Barrett J. C., Schlegel R. Transcriptional activation of the telomerase hTERT gene by human papillomavirus type 16 E6 oncoprotein. J Virol. 2001 May;75(9):4467–4472. doi: 10.1128/JVI.75.9.4467-4472.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  144. Vonderheide R. H., Hahn W. C., Schultze J. L., Nadler L. M. The telomerase catalytic subunit is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes. Immunity. 1999 Jun;10(6):673–679. doi: 10.1016/s1074-7613(00)80066-7. [DOI] [PubMed] [Google Scholar]
  145. Wan M. S., Fell P. L., Akhtar S. Synthetic 2'-O-methyl-modified hammerhead ribozymes targeted to the RNA component of telomerase as sequence-specific inhibitors of telomerase activity. Antisense Nucleic Acid Drug Dev. 1998 Aug;8(4):309–317. doi: 10.1089/oli.1.1998.8.309. [DOI] [PubMed] [Google Scholar]
  146. White L. K., Wright W. E., Shay J. W. Telomerase inhibitors. Trends Biotechnol. 2001 Mar;19(3):114–120. doi: 10.1016/s0167-7799(00)01541-9. [DOI] [PubMed] [Google Scholar]
  147. Wisman G. B., De Jong S., Meersma G. J., Helder M. N., Hollema H., de Vries E. G., Keith W. N., van der Zee A. G. Telomerase in (pre)neoplastic cervical disease. Hum Pathol. 2000 Oct;31(10):1304–1312. doi: 10.1053/hupa.2000.19299. [DOI] [PubMed] [Google Scholar]
  148. Wright J. H., Gottschling D. E., Zakian V. A. Saccharomyces telomeres assume a non-nucleosomal chromatin structure. Genes Dev. 1992 Feb;6(2):197–210. doi: 10.1101/gad.6.2.197. [DOI] [PubMed] [Google Scholar]
  149. Wright W. E., Shay J. W., Piatyszek M. A. Modifications of a telomeric repeat amplification protocol (TRAP) result in increased reliability, linearity and sensitivity. Nucleic Acids Res. 1995 Sep 25;23(18):3794–3795. doi: 10.1093/nar/23.18.3794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  150. Wright W. E., Tesmer V. M., Huffman K. E., Levene S. D., Shay J. W. Normal human chromosomes have long G-rich telomeric overhangs at one end. Genes Dev. 1997 Nov 1;11(21):2801–2809. doi: 10.1101/gad.11.21.2801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  151. Wright W. E., Tesmer V. M., Liao M. L., Shay J. W. Normal human telomeres are not late replicating. Exp Cell Res. 1999 Sep 15;251(2):492–499. doi: 10.1006/excr.1999.4602. [DOI] [PubMed] [Google Scholar]
  152. Wu H. L., Hsu C. Y., Liu W. H., Yung B. Y. Berberine-induced apoptosis of human leukemia HL-60 cells is associated with down-regulation of nucleophosmin/B23 and telomerase activity. Int J Cancer. 1999 Jun 11;81(6):923–929. doi: 10.1002/(sici)1097-0215(19990611)81:6<923::aid-ijc14>3.0.co;2-d. [DOI] [PubMed] [Google Scholar]
  153. Xu D., Wang Q., Gruber A., Björkholm M., Chen Z., Zaid A., Selivanova G., Peterson C., Wiman K. G., Pisa P. Downregulation of telomerase reverse transcriptase mRNA expression by wild type p53 in human tumor cells. Oncogene. 2000 Oct 26;19(45):5123–5133. doi: 10.1038/sj.onc.1203890. [DOI] [PubMed] [Google Scholar]
  154. Yamaguchi F., Morrison R. S., Takahashi H., Teramoto A. Anti-telomerase therapy suppressed glioma proliferation. Oncol Rep. 1999 Jul-Aug;6(4):773–776. doi: 10.3892/or.6.4.773. [DOI] [PubMed] [Google Scholar]
  155. Yashima K., Ashfaq R., Nowak J., Von Gruenigen V., Milchgrub S., Rathi A., Albores-Saavedra J., Shay J. W., Gazdar A. F. Telomerase activity and expression of its RNA component in cervical lesions. Cancer. 1998 Apr 1;82(7):1319–1327. [PubMed] [Google Scholar]
  156. Yashima K., Milchgrub S., Gollahon L. S., Maitra A., Saboorian M. H., Shay J. W., Gazdar A. F. Telomerase enzyme activity and RNA expression during the multistage pathogenesis of breast carcinoma. Clin Cancer Res. 1998 Jan;4(1):229–234. [PubMed] [Google Scholar]
  157. Yegorov Y. E., Chernov D. N., Akimov S. S., Bolsheva N. L., Krayevsky A. A., Zelenin A. V. Reverse transcriptase inhibitors suppress telomerase function and induce senescence-like processes in cultured mouse fibroblasts. FEBS Lett. 1996 Jul 1;389(2):115–118. doi: 10.1016/0014-5793(96)00533-9. [DOI] [PubMed] [Google Scholar]
  158. Yi X., White D. M., Aisner D. L., Baur J. A., Wright W. E., Shay J. W. An alternate splicing variant of the human telomerase catalytic subunit inhibits telomerase activity. Neoplasia. 2000 Sep-Oct;2(5):433–440. doi: 10.1038/sj.neo.7900113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  159. Yokoyama Y., Takahashi Y., Shinohara A., Lian Z., Wan X., Niwa K., Tamaya T. Attenuation of telomerase activity by a hammerhead ribozyme targeting the template region of telomerase RNA in endometrial carcinoma cells. Cancer Res. 1998 Dec 1;58(23):5406–5410. [PubMed] [Google Scholar]
  160. Zhang X., Mar V., Zhou W., Harrington L., Robinson M. O. Telomere shortening and apoptosis in telomerase-inhibited human tumor cells. Genes Dev. 1999 Sep 15;13(18):2388–2399. doi: 10.1101/gad.13.18.2388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  161. Zhao J. Q., Glasspool R. M., Hoare S. F., Bilsland A., Szatmari I., Keith W. N. Activation of telomerase rna gene promoter activity by NF-Y, Sp1, and the retinoblastoma protein and repression by Sp3. Neoplasia. 2000 Nov-Dec;2(6):531–539. doi: 10.1038/sj.neo.7900114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  162. van Steensel B., Smogorzewska A., de Lange T. TRF2 protects human telomeres from end-to-end fusions. Cell. 1998 Feb 6;92(3):401–413. doi: 10.1016/s0092-8674(00)80932-0. [DOI] [PubMed] [Google Scholar]

Articles from Philosophical Transactions of the Royal Society B: Biological Sciences are provided here courtesy of The Royal Society

RESOURCES