Telomere shortening associated with chromosome instability is arrested in immortal cells which express telomerase activity.
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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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In primary cells deficient for Rb and p53, continued cellular growth beyond the Hayflick limit results in severe telomere shortening, marked genetic instability, and massive cell death-a period referred to as crisis.
“In primary cells deficient for Rb and p53, continued cellular growth beyond the Hayflick limit results in severe telomere shortening, marked genetic instability, and massive cell death—a period referred to as crisis (Counter et al. 1992”
From p53 Deficiency Rescues the Adverse Effects of Telomere Loss and Cooperates with Telomere Dysfunction to Accelerate Carcinogenesis (1999) · cites this paper as Counter et al. 1992
With further divisions, human fibroblasts continue to lose telomeres, capping fails, chromosomal instability becomes widespread, and apoptosis occurs, a state called crisis.
“However, as these human fibroblasts undergo additional cell divisions, telomere erosion continues and the loss of telomere capping function produces rampant chromosomal instability and widespread apoptosis, a cellular state termed crisis (27).”
From Telomeres and telomerase in cancer (2010) · cites this paper as [27]
Crisis serves as the second checkpoint in tumor suppression and is characterized by multiple chromosomal fusions.
“Crisis serves as the second checkpoint in tumor suppression and is characterized by multiple chromosomal fusions36.”
From Telomere dysfunction and tumour suppression: the senescence connection (2008) · cites this paper as [36]
Keeping telomeres intact is necessary for malignant cells to keep dividing.
“Telomere maintenance is essential to the replicative potential of malignant cells and the inhibition of telomerase can lead to telomere shortening and cessation of unrestrained proliferation.”
From A highly selective telomerase inhibitor limiting human cancer cell proliferation (2001) · cites this paper as Counter et al., 1992
Telomeres eventually become critically short and lose their protective function at chromosome ends.
“Eventually, telomeres shorten to a critical length and lose their ability to protect the ends of chromosomal DNA (Counter et al., 1992;Blasco et al., 1997).”
From A highly selective telomerase inhibitor limiting human cancer cell proliferation (2001) · cites this paper as Counter et al., 1992
Blocking telomerase can shorten telomeres and stop uncontrolled growth.
“Telomere maintenance is essential to the replicative potential of malignant cells and the inhibition of telomerase can lead to telomere shortening and cessation of unrestrained proliferation.”
From A highly selective telomerase inhibitor limiting human cancer cell proliferation (2001) · cites this paper as Counter et al., 1992
In cancer cells, telomerase reactivation is thought to stabilize telomere length, offset erosion, and give malignant cells unlimited proliferative capacity.
“In cancer cells, the reactivation of telomerase is thought to stabilize telomere length, thereby compensating for the cell division-related telomere erosion and providing unlimited proliferative capacity to malignant cells (Counter et al., 1992;Kim et al., 1994).”
From A highly selective telomerase inhibitor limiting human cancer cell proliferation (2001) · cites this paper as Counter et al., 1992
Most normal human cells have low or undetectable telomerase, and their telomeric DNA is lost at 30-120 bp per replication cycle.
“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 (Harley et al., 1990;Hastie et al., 1990;Counter et al., 1992).”
From A highly selective telomerase inhibitor limiting human cancer cell proliferation (2001) · cites this paper as Counter et al., 1992
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“Telomere shortening was also correlated with crisis (that is, proliferation failure and cell death) of human cells whose lifespan in culture had been temporarily extended with viral oncogenes (Counter et al. 1992).”
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“sufficient to maintain the lengths of their telomeres (12).”
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- 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)
- Venue
- The EMBO Journal
- Published
- 1992-05-01
- Volume
- 11
- Issue
- 5
- Pages
- 1921-1929
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- 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
- 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
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Agricultural and Biological Sciences › Plant Science › 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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