Human Molecular Genetics, Vol 6, 2011-2019, Copyright © 1997 by Oxford University Press
A Kilian, DD Bowtell, HE Abud, GR Hime, DJ Venter, PK Keese, EL Duncan, RR Reddel and RA Jefferson
Telomerase is a multicomponent reverse transcriptase enzyme that adds DNA
repeats to the ends of chromosomes using its RNA component as a template
for synthesis. Telomerase activity is detected in the germline as well as
the majority of tumors and immortal cell lines, and at low levels in
several types of normal cells. We have cloned a human gene homologous to a
protein from Saccharomyces cerevisiae and Euplotes aediculatus that has
reverse transcriptase motifs and is thought to be the catalytic subunit of
telomerase in those species. This gene is present in the human genome as a
single copy sequence with a dominant transcript of approximately 4 kb in a
human colon cancer cell line, LIM1215. The cDNA sequence was determined
using clones from a LIM1215 cDNA library and by RT-PCR, cRACE and 3'RACE on
mRNA from the same source. We show that the gene is expressed in several
normal tissues, telomerase-positive post-crisis (immortal) cell lines and
various tumors but is not expressed in the majority of normal tissues
analyzed, pre-crisis (non-immortal) cells and telomerase-negative immortal
(ALT) cell lines. Multiple products were identified by RT-PCR using primers
within the reverse transcriptase domain. Sequencing of these products
suggests that they arise by alternative splicing. Strikingly, various
tumors, cell lines and even normal tissues (colonic crypt and testis)
showed considerable differences in the splicing patterns. Alternative
splicing of the telomerase catalytic subunit transcript may be important
for the regulation of telomerase activity and may give rise to proteins
with different biochemical functions.
ARTICLES
Isolation of a candidate human telomerase catalytic subunit gene, which reveals complex splicing patterns in different cell types
CAMBIA, Canberra, Australia. zej@cambia.org.au
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T. J. Moriarty, S. Huard, S. Dupuis, and C. Autexier Functional Multimerization of Human Telomerase Requires an RNA Interaction Domain in the N Terminus of the Catalytic Subunit Mol. Cell. Biol., February 15, 2002; 22(4): 1253 - 1265. [Abstract] [Full Text] [PDF]
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X. Yi, J. W. Shay, and W. E. Wright Quantitation of telomerase components and hTERT mRNA splicing patterns in immortal human cells Nucleic Acids Res., December 1, 2001; 29(23): 4818 - 4825. [Abstract] [Full Text] [PDF]
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D. Bosoy and N. F. Lue Functional Analysis of Conserved Residues in the Putative "Finger" Domain of Telomerase Reverse Transcriptase J. Biol. Chem., November 30, 2001; 276(49): 46305 - 46312. [Abstract] [Full Text] [PDF]
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B. N. Armbruster, S. S. R. Banik, C. Guo, A. C. Smith, and C. M. Counter N-Terminal Domains of the Human Telomerase Catalytic Subunit Required for Enzyme Activity in Vivo Mol. Cell. Biol., November 15, 2001; 21(22): 7775 - 7786. [Abstract] [Full Text] [PDF]
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M. Krams, A. Claviez, K. Heidorn, G. Krupp, R. Parwaresch, D. Harms, and P. Rudolph Regulation of Telomerase Activity by Alternate Splicing of Human Telomerase Reverse Transcriptase mRNA in a Subset of Neuroblastomas Am. J. Pathol., November 1, 2001; 159(5): 1925 - 1932. [Abstract] [Full Text] [PDF]
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 D. X. Mason, C. Autexier, and C. W. Greider Tetrahymena proteins p80 and p95 are not core telomerase components PNAS, October 5, 2001; (2001) 221456398. [Abstract] [Full Text] [PDF]
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A.-L. Ducrest, M. Amacker, Y. D. Mathieu, A. P. Cuthbert, D. A. Trott, R. F. Newbold, M. Nabholz, and J. Lingner Regulation of Human Telomerase Activity: Repression by Normal Chromosome 3 Abolishes Nuclear Telomerase Reverse Transcriptase Transcripts but Does Not Affect c-Myc Activity Cancer Res., October 1, 2001; 61(20): 7594 - 7602. [Abstract] [Full Text] [PDF]
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W. C. Hahn Telomerase and Cancer: Where and When? Clin. Cancer Res., October 1, 2001; 7(10): 2953 - 2954. [Full Text] [PDF]
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T. L. Beattie, W. Zhou, M. O. Robinson, and L. Harrington Functional Multimerization of the Human Telomerase Reverse Transcriptase Mol. Cell. Biol., September 15, 2001; 21(18): 6151 - 6160. [Abstract] [Full Text] [PDF]
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 Y. Yokoyama, X. Wan, Y. Takahashi, A. Shinohara, and T. Tamaya Alternatively spliced variant deleting exons 7 and 8 of the human telomerase reverse transcriptase gene is dominantly expressed in the uterus Mol. Hum. Reprod., September 1, 2001; 7(9): 853 - 857. [Abstract] [Full Text] [PDF]
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J.-C. Soria, C. Moon, L. Wang, W. N. Hittelman, S. J. Jang, S.-Y. Sun, J. J. Lee, D. Liu, J. M. Kurie, R. C. Morice, et al. Effects of N-(4-Hydroxyphenyl)retinamide on hTERT Expression in the Bronchial Epithelium of Cigarette Smokers J Natl Cancer Inst, August 15, 2001; 93(16): 1257 - 1263. [Abstract] [Full Text] [PDF]
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Z. Lin, S. Lim, M. A. Viani, M. Sapp, and M. S. Lim Down-Regulation of Telomerase Activity in Malignant Lymphomas by Radiation and Chemotherapeutic Agents Am. J. Pathol., August 1, 2001; 159(2): 711 - 719. [Abstract] [Full Text]
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I. Braunstein, O. Cohen-Barak, C. Shachaf, Y. Ravel, M. Yalon-Hacohen, G. B. Mills, M. Tzukerman, and K. L. Skorecki Human Telomerase Reverse Transcriptase Promoter Regulation in Normal and Malignant Human Ovarian Epithelial Cells Cancer Res., July 1, 2001; 61(14): 5529 - 5536. [Abstract] [Full Text] [PDF]
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J. Sachsinger, E. Gonzalez-Suarez, E. Samper, R. Heicappell, M. Muller, and Maria. A. Blasco Telomerase Inhibition in RenCa, a Murine Tumor Cell Line with Short Telomeres, by Overexpression of a Dominant Negative mTERT Mutant, Reveals Fundamental Differences in Telomerase Regulation between Human and Murine Cells Cancer Res., July 1, 2001; 61(14): 5580 - 5586. [Abstract] [Full Text] [PDF]
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K. Perrem, L. M. Colgin, A. A. Neumann, T. R. Yeager, and R. R. Reddel Coexistence of Alternative Lengthening of Telomeres and Telomerase in hTERT-Transfected GM847 Cells Mol. Cell. Biol., June 15, 2001; 21(12): 3862 - 3875. [Abstract] [Full Text]
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F. Pendino, M. Flexor, F. Delhommeau, D. Buet, M. Lanotte, and E. Ségal-Bendirdjian Retinoids down-regulate telomerase and telomere length in a pathway distinct from leukemia cell differentiation PNAS, May 18, 2001; (2001) 111464998. [Abstract] [Full Text]
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F. Bachand and C. Autexier Functional Regions of Human Telomerase Reverse Transcriptase and Human Telomerase RNA Required for Telomerase Activity and RNA-Protein Interactions Mol. Cell. Biol., March 1, 2001; 21(5): 1888 - 1897. [Abstract] [Full Text]
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C. K. Lai, J. R. Mitchell, and K. Collins RNA Binding Domain of Telomerase Reverse Transcriptase Mol. Cell. Biol., February 15, 2001; 21(4): 990 - 1000. [Abstract] [Full Text]
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M. J. O'Hare, J. Bond, C. Clarke, Y. Takeuchi, A. J. Atherton, C. Berry, J. Moody, A. R. J. Silver, D. C. Davies, A. E. Alsop, et al. Conditional immortalization of freshly isolated human mammary fibroblasts and endothelial cells PNAS, January 16, 2001; 98(2): 646 - 651. [Abstract] [Full Text] [PDF]
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V. Rohde, H.-P. Sattler, T. Bund, H. Bonkhoff, T. Fixemer, C. Bachmann, R. Lensch, G. Unteregger, M. Stoeckle, and B. Wullich Expression of the Human Telomerase Reverse Transcriptase Is Not Related to Telomerase Activity in Normal and Malignant Renal Tissue Clin. Cancer Res., December 1, 2000; 6(12): 4803 - 4809. [Abstract] [Full Text]
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Y. Liu, B. E. Snow, M. P. Hande, G. Baerlocher, V. A. Kickhoefer, D. Yeung, A. Wakeham, A. Itie, D. P. Siderovski, P. M. Lansdorp, et al. Telomerase-Associated Protein TEP1 Is Not Essential for Telomerase Activity or Telomere Length Maintenance In Vivo Mol. Cell. Biol., November 1, 2000; 20(21): 8178 - 8184. [Abstract] [Full Text]
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A. Zhang, C. Zheng, C. Lindvall, M. Hou, J. Ekedahl, R. Lewensohn, Z. Yan, X. Yang, M. Henriksson, E. Blennow, et al. Frequent Amplification of the Telomerase Reverse Transcriptase Gene in Human Tumors Cancer Res., November 1, 2000; 60(22): 6230 - 6235. [Abstract] [Full Text]
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T. L. Beattie, W. Zhou, M. O. Robinson, and L. Harrington Polymerization Defects within Human Telomerase Are Distinct from Telomerase RNA and TEP1 Binding Mol. Biol. Cell, October 1, 2000; 11(10): 3329 - 3340. [Abstract] [Full Text]
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 M. Arinaga, S. Shimizu, K. Gotoh, N. Haruki, T. Takahashi, T. Takahashi, and T. Mitsudomi Expression of human telomerase subunit genes in primary lung cancer and its clinical significance Ann. Thorac. Surg., August 1, 2000; 70(2): 401 - 405. [Abstract] [Full Text] [PDF]
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J. Xia, Y. Peng, I. S. Mian, and N. F. Lue Identification of Functionally Important Domains in the N-Terminal Region of Telomerase Reverse Transcriptase Mol. Cell. Biol., July 15, 2000; 20(14): 5196 - 5207. [Abstract] [Full Text]
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M. Meyerson Role of Telomerase in Normal and Cancer Cells J. Clin. Oncol., July 1, 2000; 18(13): 2626 - 2634. [Abstract] [Full Text] [PDF]
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S. Misiti, S. Nanni, G. Fontemaggi, Y.-S. Cong, J. Wen, H. W. Hirte, G. Piaggio, A. Sacchi, A. Pontecorvi, S. Bacchetti, et al. Induction of hTERT Expression and Telomerase Activity by Estrogens in Human Ovary Epithelium Cells Mol. Cell. Biol., June 1, 2000; 20(11): 3764 - 3771. [Abstract] [Full Text]
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H. Niida, Y. Shinkai, M. P. Hande, T. Matsumoto, S. Takehara, M. Tachibana, M. Oshimura, P. M. Lansdorp, and Y. Furuichi Telomere Maintenance in Telomerase-Deficient Mouse Embryonic Stem Cells: Characterization of an Amplified Telomeric DNA Mol. Cell. Biol., June 1, 2000; 20(11): 4115 - 4127. [Abstract] [Full Text]
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 I. Savre-Train, L. S. Gollahon, and S. E. Holt Clonal Heterogeneity in Telomerase Activity and Telomere Length in Tumor-Derived Cell Lines Experimental Biology and Medicine, April 1, 2000; 223(4): 379 - 388. [Abstract] [Full Text] [PDF]
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C. Günes, S. Lichtsteiner, A. P. Vasserot, and C. Englert Expression of the hTERT Gene Is Regulated at the Level of Transcriptional Initiation and Repressed by Mad1 Cancer Res., April 1, 2000; 60(8): 2116 - 2121. [Abstract] [Full Text]
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 J. B. de Kok, T. J.M. Ruers, G. N.P. van Muijen, A. van Bokhoven, H. L. Willems, and D. W. Swinkels Real-Time Quantification of Human Telomerase Reverse Transcriptase mRNA in Tumors and Healthy Tissues Clin. Chem., March 1, 2000; 46(3): 313 - 318. [Abstract] [Full Text] [PDF]
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 M. M. Ouellette, L. D. McDaniel, W. E. Wright, J. W. Shay, and R. A. Schultz The establishment of telomerase-immortalized cell lines representing human chromosome instability syndromes Hum. Mol. Genet., February 12, 2000; 9(3): 403 - 411. [Abstract] [Full Text] [PDF]
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F. Bachand and C. Autexier Functional Reconstitution of Human Telomerase Expressed in Saccharomyces cerevisiae J. Biol. Chem., December 31, 1999; 274(53): 38027 - 38031. [Abstract] [Full Text] [PDF]
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S. Oh, Y. Song, J. Yim, and T. K. Kim The Wilms' Tumor 1 Tumor Suppressor Gene Represses Transcription of the Human Telomerase Reverse Transcriptase Gene J. Biol. Chem., December 24, 1999; 274(52): 37473 - 37478. [Abstract] [Full Text] [PDF]
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M. S. Fitzgerald, K. Riha, F. Gao, S. Ren, T. D. McKnight, and D. E. Shippen Disruption of the telomerase catalytic subunit gene from Arabidopsis inactivates telomerase and leads to a slow loss of telomeric DNA PNAS, December 21, 1999; 96(26): 14813 - 14818. [Abstract] [Full Text] [PDF]
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 J.-P. LIU Studies of the molecular mechanisms in the regulation of telomerase activity FASEB J, December 1, 1999; 13(15): 2091 - 2104. [Abstract] [Full Text]
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 K. L. Friedman and T. R. Cech Essential functions of amino-terminal domains in the yeast telomerase catalytic subunit revealed by selection for viable mutants Genes & Dev., November 1, 1999; 13(21): 2863 - 2874. [Abstract] [Full Text]
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K. Aogi, K. Kitahara, V. Urquidi, D. Tarin, and S. Goodison Comparison of Telomerase and CD44 Expression as Diagnostic Tumor Markers in Lesions of the Thyroid Clin. Cancer Res., October 1, 1999; 5(10): 2790 - 2797. [Abstract] [Full Text] [PDF]
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X. Zhang, V. Mar, W. Zhou, L. Harrington, and M. O. Robinson Telomere shortening and apoptosis in telomerase-inhibited human tumor cells Genes & Dev., September 15, 1999; 13(18): 2388 - 2399. [Abstract] [Full Text]
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V. M. Tesmer, L. P. Ford, S. E. Holt, B. C. Frank, X. Yi, D. L. Aisner, M. Ouellette, J. W. Shay, and W. E. Wright Two Inactive Fragments of the Integral RNA Cooperate To Assemble Active Telomerase with the Human Protein Catalytic Subunit (hTERT) In Vitro Mol. Cell. Biol., September 1, 1999; 19(9): 6207 - 6216. [Abstract] [Full Text] [PDF]
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C. A. Brenner, Y. M. Wolny, R. R. Adler, and J. Cohen Alternative splicing of the telomerase catalytic subunit in human oocytes and embryos Mol. Hum. Reprod., September 1, 1999; 5(9): 845 - 850. [Abstract] [Full Text] [PDF]
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J. S. Dome, S. Chung, T. Bergemann, C. B. Umbricht, M. Saji, L. A. Carey, P. E. Grundy, E. J. Perlman, N. E. Breslow, and S. Sukumar High Telomerase Reverse Transcriptase (hTERT) Messenger RNA Level Correlates with Tumor Recurrence in Patients with Favorable Histology Wilms' Tumor Cancer Res., September 1, 1999; 59(17): 4301 - 4307. [Abstract] [Full Text] [PDF]
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J.-i. Hisatake, T. Kubota, Y. Hisatake, M. Uskokovic, S. Tomoyasu, and H. P. Koeffler 5,6-trans-16-ene-Vitamin D3: A New Class of Potent Inhibitors of Proliferation of Prostate, Breast, and Myeloid Leukemic Cells Cancer Res., August 1, 1999; 59(16): 4023 - 4029. [Abstract] [Full Text] [PDF]
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P. Yan, J.-M. Coindre, J. Benhattar, F. T. Bosman, and L. Guillou Telomerase Activity and Human Telomerase Reverse Transcriptase mRNA Expression in Soft Tissue Tumors: Correlation with Grade, Histology, and Proliferative Activity Cancer Res., July 1, 1999; 59(13): 3166 - 3170. [Abstract] [Full Text] [PDF]
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X. Yi, V. M. Tesmer, I. Savre-Train, J. W. Shay, and W. E. Wright Both Transcriptional and Posttranscriptional Mechanisms Regulate Human Telomerase Template RNA Levels Mol. Cell. Biol., June 1, 1999; 19(6): 3989 - 3997. [Abstract] [Full Text] [PDF]
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 A. MOSQUERA, J. L. FERNÁNDEZ, A. CAMPOS, V. J GOYANES, J. RAMIRO-DÍAZ, and J. GOSÁLVEZ Simultaneous decrease of telomere length and telomerase activity with ageing of human amniotic fluid cells J. Med. Genet., June 1, 1999; 36(6): 494 - 496. [Full Text]
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M. Saji, S. Xydas, W. H. Westra, C.-K. Liang, D. P. Clark, R. Udelsman, C. B. Umbricht, S. Sukumar, and M. A. Zeiger Human Telomerase Reverse Transcriptase (hTERT) Gene Expression in Thyroid Neoplasms Clin. Cancer Res., June 1, 1999; 5(6): 1483 - 1489. [Abstract] [Full Text] [PDF]
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K. Liu, M. M. Schoonmaker, B. L. Levine, C. H. June, R. J. Hodes, and N.-p. Weng Constitutive and regulated expression of telomerase reverse transcriptase (hTERT) in human lymphocytes PNAS, April 27, 1999; 96(9): 5147 - 5152. [Abstract] [Full Text] [PDF]
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H. Vaziri, J. A. Squire, T. K. Pandita, G. Bradley, R. M. Kuba, H. Zhang, S. Gulyas, R. P. Hill, G. P. Nolan, and S. Benchimol Analysis of Genomic Integrity and p53-Dependent G1 Checkpoint in Telomerase-Induced Extended-Life-Span Human Fibroblasts Mol. Cell. Biol., March 1, 1999; 19(3): 2373 - 2379. [Abstract] [Full Text] [PDF]
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 M. P. Hande, E. Samper, P. Lansdorp, and M. A. Blasco Telomere Length Dynamics and Chromosomal Instability in Cells Derived from Telomerase Null Mice J. Cell Biol., February 22, 1999; 144(4): 589 - 601. [Abstract] [Full Text] [PDF]
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A. P. Cuthbert, J. Bond, D. A. Trott, S. Gill, J. Broni, A. Marriott, G. Khoudoli, E. K. Parkinson, C. S. Cooper, and R. F. Newbold Telomerase Repressor Sequences on Chromosome 3 and Induction of Permanent Growth Arrest in Human Breast Cancer Cells J Natl Cancer Inst, January 6, 1999; 91(1): 37 - 45. [Abstract] [Full Text] [PDF]
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H. Kiaris and A. V. Schally Decrease in telomerase activity in U-87MG human glioblastomas after treatment with an antagonist of growth hormone-releasing hormone PNAS, January 5, 1999; 96(1): 226 - 231. [Abstract] [Full Text] [PDF]
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H. Li, L. Zhao, Z. Yang, J. W. Funder, and J.-P. Liu Telomerase Is Controlled by Protein Kinase Calpha in Human Breast Cancer Cells J. Biol. Chem., December 11, 1998; 273(50): 33436 - 33442. [Abstract] [Full Text] [PDF]
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