Telomeres and Telomerase in Ageing and Cancer

Abstract

Telomeres protect the ends of chromosomes and shorten each time somatic human cells divide. As a consequence, cells enter senescence after a limited number of divisions. The enzyme telomerase expressed in cancer cells and renewal tissues can prevent the shortening of telomeres and extend cellular lifespan.

Keywords: telomere; telomerase; cancer; ageing

Figure 1.

Biochemical activity of telomerase. The enzyme telomerase is made of two essential subunits, human telomerase reverse transcriptase (hTERT) and human telomerase RNA (hTR). The hTR RNA contains a short sequence, complementary to that of the telomeric repeats (5′‐CUAACCCUAA‐3′), which the enzyme uses as a template. As the enzyme associates with the telomeres, this sequence hybridizes with the 30 overhang that caps all telomeres. The protein hTERT, acting as a reverse transcriptase, then uses the telomere as a primer and hTR as a template to synthesize a six‐base telomeric repeat. The enzyme is highly processive and can add many repeats to the same DNA substrate through cycles of synthesis and translocation.

Figure 2.

Mortality stages 1 and 2. Most somatic human cells lack telomerase, and as a consequence, shorten their telomeres at each round of cell divisions. When the shortest telomere reaches a threshold size, Mortality Stage 1 (M1 or Senescence) is triggered. The cell cycle arrest that characterizes M1 is maintained by the activities of p53 and RB, and can therefore be bypassed by the loss of these tumour suppressors. Cells that have overcome M1 continue to shorten their telomeres as they divide, until the induction of Mortality stage 2 (M2 or crisis). M2 is characterized by massive cell death and is due to terminal telomere shortening. Rare cells can escape M2 to give rise to immortal clones, but only after telomeres have become stabilized through either telomerase (hTERT) expression or activation of the ALT pathway.

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References

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Further Reading

Lansdorp PM (2006) Stress, social rank and leukocyte telomere length. Aging Cell 5: 583–584.

Sharpless NE and DePinho RA (2004) Telomeres, stem cells, senescence, and cancer. Journal of Clinical Investigation 113: 160–168.

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Wright WE and Shay JW (2000) Telomere dynamics in cancer progression and prevention: fundamental differences in human and mouse telomere biology. Nature Medicine 6: 849–851.

Web Links

TelDB: GenLink Multimedia Telomere Resource. TelDB is a telomere information centre that provides access to a searchable database of more than 2100 telomere‐related citations from 290 journals. At: http://www.genlink.wustl.edu/teldb/

Telomerase RNA component (TERC) and Telomerase reverse transcriptase (TERT); GeneID 7012 and 7015, respectively, at Entrez Gene: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=gene

Telomerase RNA component (TERC) and Telomerase reverse transcriptase (TERT); MIM number 602322 and 187270, respectively, at OMIM: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=omim

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How to Cite close
Ouellette, Michel M, and Choi, Kyung Hyun(Sep 2007) Telomeres and Telomerase in Ageing and Cancer. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0006067.pub2]