Cited by 2,096Telomeres, Telomerase, and SenescenceGenetics, Aging, and Longevity in Model OrganismsChromosomal and Genetic Variations

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Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity.

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Counter, C.M., Avilion, A.A., LeFeuvre, C.E., Stewart, N.G., Greider, C.W., Harley, C.B., Bacchetti, S.·1992·The EMBO Journal

DOI 10.1002/j.1460-2075.1992.tb05245.xPMC PMC556651

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Abstract

Loss of telomeric DNA during cell proliferation may play a role in ageing and cancer. Since telomeres permit complete replication of eukaryotic chromosomes and protect their ends from recombination, we have measured telomere length, telomerase activity and chromosome rearrangements in human cells before and after transformation with SV40 or Ad5. In all mortal populations, telomeres shortened by approximately 65 bp/generation during the lifespan of the cultures. When transformed cells reached crisis, the length of the telomeric TTAGGG repeats was only approximately 1.5 kbp and many dicentric chromosomes were observed. In immortal cells, telomere length and frequency of dicentric chromosomes stabilized after crisis. Telomerase activity was not detectable in control or extended lifespan populations but was present in immortal populations. These results suggest that chromosomes with short (TTAGGG)n tracts are recombinogenic, critically shortened telomeres may be incompatible with cell proliferation and stabilization of telomere length by telomerase may be required for immortalization.

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A new technique for the assay of infectivity of human adenovirus 5 DNA
Graham, F. L., & van der Eb, A. J. (1973) · Virology · doi:10.1016/0042-6822(73)90341-3 · Cited by 9,302
Telomeres shorten during ageing of human fibroblasts
Harley, C. B., Futcher, A. B., & Greider, C. W. (1990) · Nature · doi:10.1038/345458a0 · Cited by 5,750
Self-citation
Characteristics of a human cell line transformed by DNA from human adenovirus type 5
Graham, F. L., Russell, W. C., Smiley, J., & Nairn, R. (1977) · Journal of General Virology · doi:10.1099/0022-1317-36-1-59 · Cited by 4,793
Structure and function of telomeres
Blackburn, E. H. (1991) · Nature · doi:10.1038/350569a0 · Cited by 3,596
Identification of a specific telomere terminal transferase activity in tetrahymena extracts
Greider, C. W., & Blackburn, E. H. (1985) · Cell · doi:10.1016/0092-8674(85)90170-9 · Cited by 3,400
Self-citation
Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter.
Southern, P. J., & Berg, P. R. (1982) · PubMed · Cited by 2,740
A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes.
Moyzis, R. K., Buckingham, J. M., Cram, L. S., Dani, M. A. C., Deaven, L. L., Jones, M. D., Meyne, J., Ratliff, R. L., & Wu, J. R. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.18.6622 · Cited by 2,326
Untitled work
Olovnikov (1973) · doi:10.1016/0022-5193(73)90198-7 · Cited by 1,847
Telomere reduction in human colorectal carcinoma and with ageing
Hastie, N. D., Dempster, M., Dunlop, M. G., Thompson, A. M., Green, D. K., & Allshire, R. C. (1990) · Nature · doi:10.1038/346866a0 · Cited by 1,650
A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis
Greider, C. W., & Blackburn, E. H. (1989) · Nature · doi:10.1038/337331a0 · Cited by 1,643
Self-citation

Show all 53 references

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“Hybridization and washing were carried out as described.(23) The gel was autoradiographed on Kodak XAR-5 X-ray film for 12-24 h at room temperature.”
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Kokhaei, P., Palma, M., Hansson, L., Österborg, A., Mellstedt, H., & Choudhury, A. (2007) · Experimental Hematology · doi:10.1016/j.exphem.2006.10.006 · Cited by 60
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Anderson, S., Shera, K. A., Ihle, J., Billman, L., Goff, B. A., Greer, B. E., Tamimi, H. K., McDougall, J. K., & Klingelhutz, A. J. (1997) · Europe PMC (PubMed Central) · Cited by 60
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Chang, S. S., & DePinho, R. A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.212514699 · Cited by 61
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Uehara, H., Nardone, G., Nazarenko, I. A., & Hohman, R. J. (1999) · BioTechniques · doi:10.2144/99263pf01 · Cited by 61
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Smith, C. D., & Blackburn, E. H. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.145.2.203 · Cited by 60
“Cells lacking either the TER gene or telomerase activity experience progressive telomere shortening with each cell division (Lundblad and Szostak, 1989; Counter et al., 1992; Singer and Gottschling, 1994; McEachern and Blackburn, 1995; Bodnar et al., 1998) until telomeric DNA is reduced below a critical length, result…”
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“Immortalization of tumor cells usually requires the induction and activation of telomerase to maintain telomere length and integrity and to prevent DNA damage responses [54].”
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Illeperuma, R. P., Park, Y. J., Kim, J. M., Bae, J. Y., Che, Z. M., Son, H. K., Han, M. R., Kim, K., & Kim, J. (2011) · Journal of Materials Science Materials in Medicine · doi:10.1007/s10856-011-4473-6 · Cited by 59
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The role of telomere trimming in normal telomere length dynamics
Pickett, H. A., & Reddel, R. R. (2012) · Cell Cycle · doi:10.4161/cc.19632 · Cited by 61
Establishment of an Immortalized Human Hepatic Stellate Cell Line to Develop Antifibrotic Therapies
Shibata, N., Watanabe, T., Okitsu, T., Sakaguchi, M., Takesue, M., Kunieda, T., Omoto, K., Yamamoto, S., Tanaka, N., & Kobayashi, N. (2003) · Cell Transplantation · doi:10.3727/000000003108747064 · Cited by 59
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“Thus, telomerase reactivation is thought to be essential for the stabilization of TL in order to attain cellular immortality in human carcinogenesis [3, 21].”
Background
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Vaziri, H., & Benchimol, S. (1999) · Oncogene · doi:10.1038/sj.onc.1203016 · Cited by 59
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Background
ASSOCIATION BETWEEN OUTCOME AND TELOMERE DNA CONTENT IN PROSTATE CANCER
DONALDSON, L., Fordyce, C., Gilliland, F. D., Smith, A. Y., Feddersen, R. M., Joste, N. E., Moyzis, R. K., & Griffith, J. K. (1999) · The Journal of Urology · doi:10.1016/s0022-5347(05)68239-0 · Cited by 60
In Vitro Expansion of Human Hepatocytes is Restricted by Telomere-Dependent Replicative Aging
Wege, H., Chui, M. S., Le, H. T., Strom, S. C., & Zern, M. Α. (2003) · Cell Transplantation · doi:10.3727/000000003771000138 · Cited by 59
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Sharma, S., Raymond, É., Soda, H., Sun, D., Hilsenbeck, S., Sharma, A., Izbicka, E., Windle, B. E., & Hoff, D. D. V. (1997) · Annals of Oncology · doi:10.1023/a:1008206420505 · Cited by 59
“Experimental studies with human cells have revealed that replicative potential of cultured fibroblasts is directly proportional to mean TRF length [39] and chromosomes with critically shortened telomeric tracts may be incompatible with cellular proliferation and may require telomerase [39, 40].”
Background
Phosphatidylinositol 3-kinase related kinases
Abraham, R. T. (1996) · Current Opinion in Immunology · doi:10.1016/s0952-7915(96)80132-4 · Cited by 58
Chromothripsis during telomere crisis is independent of NHEJ, and consistent with a replicative originPreprint
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Background
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Senescence and epigenetic dysregulation in cancer
Neumeister, P., Albanese, C., Balent, B., Greally, J., & Pestell, R. G. (2002) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(02)00079-1 · Cited by 56
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BackgroundMethod
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Kim, J. H., Kim, J. H., Lee, G. E., Kim, S. W., & Chung, I. K. (2003) · Biochemical Journal · doi:10.1042/bj20030363 · Cited by 54
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Uchida, N., Otsuka, T., Arima, F., Shigematsu, H., Fukuyama, T., Maeda, M., Sugio, Y., Itoh, Y., & Niho, Y. (1999) · Leukemia Research · doi:10.1016/s0145-2126(98)00170-2 · Cited by 57
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Background
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Background
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“…that contain sufficient levels of ARTICLE IN PRESS www.elsevier.com/locate/yjtbi 0022-5193/$ -see front matter r 2005 Published by Elsevier Ltd. doi:10.1016/j.jtbi.2004.12.016 telomerase, such as stem cells and germ cells, can generally maintain a constant telomere length (Counter et al., 1992).”
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“M1) and, ultimately, genetic instability if cells are driven to crisis (block M2) [3].”
Background
SV40-Mediated Immortalization
Ozer, H. L. (1999) · Progress in molecular and subcellular biology · doi:10.1007/978-3-662-06227-2_6 · Cited by 54
Models of initiation of replicative senescence by loss of telomeric DNA
Allsopp, R. (1996) · Experimental Gerontology · doi:10.1016/0531-5565(95)02008-x · Cited by 54
Telomere dysfunction: multiple paths to the same end
Harrington, L. A., & Robinson, M. O. (2002) · Oncogene · doi:10.1038/sj.onc.1205084 · Cited by 54
“…was gleaned Oncogene (2002) 21, 592 ± 597 ã 2002 Nature Publishing Group All rights reserved 0950 ± 9232/02 $25.00 www.nature.com/onc *Correspondence: MO Robinson; E-mail: mrobinso@amgen.com from following the fate of SV40-transformed human embryonic kidney cells (Counter et al., 1992).”
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Kim, W. T., Hennick, K. M., Johnson, J. Z., Finnerty, B., Choo, S.-A. S., Short, S. B., Drubin, C. W., Forster, R. E., McMaster, M. L., & Hockemeyer, D. F. (2021) · The EMBO Journal · doi:10.15252/embj.2020107346 · Cited by 55
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Cell Immortality: In Vitro Effective Techniques to Achieve and Investigate Its Applications and Challenges
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“…in the telomerase enzyme, which had recently been discovered in the single-cell Life 2024 , 14 , 417 6 of 22 Several reports confirmed the decrease in average telomere length with cell division in fibroblasts [6,57,58] and with age in somatic blood and colon cells [59], but not in germ cells.”
Background
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Clark, A., Burl, S., Denning, C. N., & Dickinson, P. (2000) · Transgenic Research · doi:10.1023/a:1008974616402 · Cited by 53
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Background
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Wang, Z., Kyo, S., Maida, Y., Takakura, M., Tanaka, M., Yatabe, N., Kanaya, T., Nakamura, M., Koike, K., Hisamoto, K., et al. (2002) · Oncogene · doi:10.1038/sj.onc.1205463 · Cited by 53
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Background
Functional evidence for a telomerase repressor gene on human chromosome 10p15.1
Nishimoto, A., Miura, N., Horikawa, I., Kugoh, H., Murakami, Y., Hirohashi, S., Kawasaki, H., Gazdar, A. F., Shay, J. W., Barrett, J. C., et al. (2001) · Oncogene · doi:10.1038/sj.onc.1204165 · Cited by 53
“Telomerase activity is detected in most human cancers and immortalized cells (Counter et al., 1992; de Lange, 1994; Kim et al., 1994).”
Background
Telomerase activity in benign and malignant thyroid diseases
Yashima, K., Vuitch, F., Gazdar, A. F., & Fahey, T. J. (1997) · Surgery · doi:10.1016/s0039-6060(97)90220-8 · Cited by 53
The N-terminus of hTERT contains a DNA-binding domain and is required for telomerase activity and cellular immortalization
Sealey, D., Zheng, L., Taboski, M. A. S., Cruickshank, J., Ikura, M., & Harrington, L. A. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp1160 · Cited by 53
“Recombinant Trx-HIS6hTERT(1–200) was mixed with radiolabeled single-stranded DNA oligonucleotides containing three full telomeric repeats and subjected to native polyacrylamide gel electrophoresis.”
Influential
Catalytically active human telomerase mutants with allele-specific biological properties
Kim, M. (2003) · Experimental Cell Research · doi:10.1016/s0014-4827(03)00217-9 · Cited by 51
Telomerase: Dr Jekyll or Mr Hyde?
Prescott, J. C., & Blackburn, E. H. (1999) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(99)80055-0 · Cited by 52
Toward a molecular understanding of human breast cancer: A hypothesis
Shay, J. W., Wright, W. E., & Werbin, H. (1993) · Breast Cancer Research and Treatment · doi:10.1007/bf00662404 · Cited by 51
“Since telomerase activity is not present in somatic cells but is present in immortal and tumorigenic cells [19], it is likely that the restoration/activation of telomerase activity is important in the immortalization of cells.”
Background
Telomeres, Telomerase and Chromosome Stability
Preston, R. J. (1997) · Radiation Research · doi:10.2307/3579618 · Cited by 53
Telomerase Activity in Reactive and Neoplastic Lymphoid Tissues: Infrequent Detection of Activity in Hodgkin's Disease
Brousset, P., Saati, T. A., Chaouche, N., Zenou, R. C., Schlaifer, D., Chittal, S. M., & Delsol, G. (1997) · Blood · doi:10.1182/blood.v89.1.26 · Cited by 52
Lead Exposure Induces Telomere Instability in Human Cells
Pottier, G., Viau, M., Ricoul, M., Shim, G., Bellamy, M., Cuceu, C., Hempel, W. M., & Sabatier, L. (2013) · PLoS ONE · doi:10.1371/journal.pone.0067501 · Cited by 51
“A correlation between reduced telomere length and dicentric chromosome frequency has been demonstrated in human senescent fibroblasts [14].”
Background
Catastrophic Endgames: Emerging Mechanisms of Telomere-Driven Genomic Instability
Cleal, K., & Baird, D. M. (2020) · Trends in Genetics · doi:10.1016/j.tig.2020.02.001 · Cited by 54
“The loss of telomeres during this extended replicative period is accompanied by a progressive increase in the frequency of telomere fusion events [17, 18].”
Background
Telomerase-Immortalized Sheep Fibroblasts Can Be Reprogrammed by Nuclear Transfer to Undergo Early Development1
Cui, W., Wylie, D., Aslam, S., Dinnyés, A., King, T., Wilmut, I., & Clark, A. J. (2003) · Biology of Reproduction · doi:10.1095/biolreprod.102.013250 · Cited by 51
TELOMERASE ACTIVATOR1 Induces Telomerase Activity and Potentiates Responses to Auxin in Arabidopsis
Ren, S., Johnston, J. S., Shippen, D. E., & McKnight, T. D. (2004) · The Plant Cell · doi:10.1105/tpc.104.025072 · Cited by 51
“A similar situation is seen in telomerasepositive immortalizedhumancells (Counter et al., 1992;Kimet al., 1994), where telomeres are not perceptibly extended.”
Background
Influence of Methotrexate Dose Intensity on Outcome of Patients with High Grade Osteogenic Osteosarcoma
Bielack, S., Beron, G., & Winkler, K. (1997) · Cancer · doi:10.1002/(sici)1097-0142(19970801)80:3 · Cited by 37
Telomerase activity in cervical cancer is quantitatively distinct from that in its precursor lesions
Kyo, S., Takakura, M., Tanaka, M., Kanaya, T., & Inoue, M. (1998) · International Journal of Cancer · doi:10.1002/(sici)1097-0215(19980220)79:1 · Cited by 51
The Asian-American E6 Variant Protein of Human Papillomavirus 16 Alone Is Sufficient To Promote Immortalization, Transformation, and Migration of Primary Human Foreskin Keratinocytes
Niccoli, S., Abraham, S., Richard, C., & Zehbe, I. (2012) · Journal of Virology · doi:10.1128/jvi.01512-12 · Cited by 49
Senescence: an antiviral defense that is tumor suppressive?
Reddel, R. R. (2009) · Carcinogenesis · doi:10.1093/carcin/bgp274 · Cited by 52
Telomeres and genomic evolution
Baird, D. M. (2018) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2016.0437 · Cited by 51
“components of the Tp53 and RB pathways, can continue to divide and undergo further telomere erosion [36].”
Karyotype instability and anchorage-independent growth in telomerase-immortalized fibroblasts from two centenarian individuals
Mondello, C., Chiesa, M., Rebuzzini, P., Zongaro, S., Verri, A., Colombo, T., Giulotto, E., D’Incalci, M., Franceschi, C., & Nuzzo, F. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(03)01484-0 · Cited by 50
Telomerase activity in head and neck tumors after introduction of wild-type p53, p21, p16, and E2F-1 genes by means of recombinant adenovirus
Henderson, Y. C., Breau, R. L., Liu, T.-J., & Clayman, G. L. (2000) · Head & Neck · doi:10.1002/1097-0347(200007)22:4 · Cited by 52
Rb and E2F-1 regulate telomerase activity in human cancer cells
Crowe, D. L., & Nguyen, D. C. (2001) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/s0167-4781(00)00296-7 · Cited by 51
Telomere attrition predominantly occurs in precursor lesions during in vivo carcinogenic process of the uterine cervix
Zhang, A., Wang, J., Zheng, B., Fang, X., Ångström, T., Liu, C., Li, X., Erlandsson, F., Björkholm, M., Nordenskjörd, M., et al. (2004) · Oncogene · doi:10.1038/sj.onc.1207527 · Cited by 50
Telomerase activity in primary and secondary glioblastomas multiforme as a novel molecular tumor marker
Harada, K., Kurisu, K., Tahara, H., Tahara, E., Ide, T., & 田原, 榮. (2000) · Journal of neurosurgery · doi:10.3171/jns.2000.93.4.0618 · Cited by 50
Telomere Length as a Tool to Monitor Satellite Cell Amplification for Cell-Mediated Gene Therapy
Decary, S., Mouly, V., & Butler-Browne, G. S. (1996) · Human Gene Therapy · doi:10.1089/hum.1996.7.11-1347 · Cited by 50
“It has been well established that the length of telomeric D NA decreases as human somatic cells divide (e.g., fibroblasts, blood lympho cytes, embryonic kidney cells, and endothelial ceUs) (Harley al, 1990; Hastie et al, 1990; Counter et al, 1992; Chang and Harley, 1995).”
Telomerase activity in the testis of infertile patients with selected causes
Fujisawa, M., Tanaka, H., Tatsumi, N., Okada, H., Arakawa, S., & Kamidono, S. (1998) · Human Reproduction · doi:10.1093/humrep/13.6.1476 · Cited by 50
“Sertoli cell-only testes without germ cells showed no telomerase activity.”
Background
Induction of telomerase activity and chromosome aberrations in human tumour cell lines following X-irradiation
Joo, O. H., Hande, M. P., Lansdorp, P. M., & Natarajan, A. T. (1998) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/s0027-5107(97)00321-7 · Cited by 50
Viral oncogenes accelerate conversion to immortality of cultured conditionally immortal human mammary epithelial cells
Garbe, J. C., Wong, M. P., Wigington, D., Yaswen, P., & Stampfer, M. R. (1999) · Oncogene · doi:10.1038/sj.onc.1202523 · Cited by 50
“Since EL cell telomeres continue to shorten with passage (Counter et al., 1992, 1994), while the immortally transformed cell lines show telomerase activity and stabilized telomere length, it has been postulated that this mutation involves reactivation of telomerase activity.”
Background
Reflections on Telomeres, Growth, Aging, and Essential Hypertension
Aviv, A., & Aviv, H. (1997) · Hypertension · doi:10.1161/01.hyp.29.5.1067 · Cited by 50
Telomerase activity and telomere length in thyroid neoplasia: biological and clinical implications
Matthews, P., Jones, C. J., Skinner, J. W., Haughton, M. F., Micco, C. D., & Wynford‐Thomas, D. (2001) · The Journal of Pathology · doi:10.1002/path.848 · Cited by 48
“Such tumours would conform to the classic model [41] in which, after an initial period of telomere erosion, telomerase activity is acquired (usually through expression of hTERT) in time to stabilize telomere length at a level above the critical threshold required for cell survival.”
Background
The Rb-Related p130 Protein Controls Telomere Lengthening through an Interaction with a Rad50-Interacting Protein, RINT-1
Kong, L.-J., Meloni, A. R., & Nevins, J. R. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.02.016 · Cited by 48
Nonhistone targets of KAT2A and KAT2B implicated in cancer biology
Bondy‐Chorney, E., Denoncourt, A. M., Sai, Y., & Downey, M. (2018) · Biochemistry and Cell Biology · doi:10.1139/bcb-2017-0297 · Cited by 50
Induction of senescence in cancer cells by the G‐quadruplex stabilizer, BMVC4, is independent of its telomerase inhibitory activity
Huang, F., Chang, C., Wang, J., Chang, T., & Lin, J. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2012.01997.x · Cited by 50
“In most normal human cells, telomerase activity is low or not detectable, and telomeric DNA is progressively lost at a rate of 30–120 bp with each replication cycle (Hastie et al., 1990; Counter et al., 1992).”
BackgroundInfluential
Cell Senescence in Human Aging and Disease
Fossel, M. (2002) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2002.tb02078.x · Cited by 49
Consequences of Telomerase Inhibition by BIBR1532 on Proliferation and Chemosensitivity of Chondrosarcoma Cell Lines
Parsch, D., Brassat, U., Brümmendorf, T. H., & Fellenberg, J. (2008) · Cancer Investigation · doi:10.1080/07357900802072905 · Cited by 49
Telomere Dysfunction in Nonalcoholic Fatty Liver Disease and Cryptogenic Cirrhosis
Laish, I., Mannasse-Green, B., Hadary, R., Biron‐Shental, T., Konikoff, F. M., Amiel, A., & Kitay‐Cohen, Y. (2016) · Cytogenetic and Genome Research · doi:10.1159/000454654 · Cited by 51
Oxidative Damage Generated by an Oxo-Metalloporphyrin onto the Human Telomeric Sequence
Vialas, C., Pratviel, G., & Meunier, B. (2000) · Biochemistry · doi:10.1021/bi000743x · Cited by 52
Mechanism of apoptosis and determination of cellular fate in chromium(VI)-exposed populations of telomerase-immortalized human fibroblasts.
Pritchard, D. E., Ceryak, S. M., Ha, L., Fornsaglio, J. L., Hartman, S. K., O’Brien, T. J., & Patierno, S. R. (2001) · PubMed · Cited by 49
Changes of telomere lengths in human intracranial tumours
N�rnberg, P., Thiel, G., Weber, F., & Epplen, J. T. (1993) · Human Genetics · doi:10.1007/bf00222724 · Cited by 49
“However, immortal cells seem to escape from progressive telomere shortening by expression of telomerase activity (Harley 1991; Counter et al. 1992).”
Background

Authors: Counter, C. M., Avilion, A. A., LeFeuvre, C. E., Stewart, N. G., Greider, C. W., Harley, C. B., & Bacchetti, S.
Affiliations: McMaster University (CA)
ORCID: Counter, C.M.
Greider, C.W.
Venue: The EMBO Journal
Publisher: Springer Science and Business Media LLC
Published: 1992-05-01
Volume: 11
Issue: 5
Pages: 1921-1929
ISSN: 0261-4189 (ISSN-L)
1460-2075
DOI: 10.1002/j.1460-2075.1992.tb05245.x
PMC: PMC556651
OpenAlex: W1543500873
Cited by: 2,096
References: 53
Citations by year: 2026: 10 · 2025: 21 · 2024: 25 · 2023: 25 · 2022: 27 · 2021: 35 · 2020: 29 · 2019: 28 · 2018: 39 · 2017: 42 · 2016: 48 · 2015: 53 · 2014: 51 · 2013: 65 · 2012: 55
FWCI: 23.80
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: The EMBO Journal (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
Keywords: telomere shortening, telomerase, chromosomal instability, cell immortalization, telomere length, dicentric chromosomes, telomeric DNA, SV40 transformation, adenovirus type 5, cell transformation, telomere recombination, cell proliferation, aging, cancer
MeSH terms: Cell Transformation, Neoplastic, Cell Transformation, Viral, Chromosomes, Human, DNA, DNA Nucleotidylexotransferase, Humans, Karyotyping, Kidney, Transfection, Telomere, Cellular Senescence

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Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity.

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