Telomeres shorten during ageing of human fibroblasts

@article{Harley1990TelomeresSD,
  title={Telomeres shorten during ageing of human fibroblasts},
  author={C. Harley and A. Futcher and C. Greider},
  journal={Nature},
  year={1990},
  volume={345},
  pages={458-460}
}
THE terminus of a DNA helix has been called its Achilles' heel1. Thus to prevent possible incomplete replication2 and instability3,4 of the termini of linear DNA, eukaryotic chromosomes end in characteristic repetitive DNA sequences within specialized structures called telomeres5. In immortal cells, loss of telomeric DNA due to degradation or incomplete replication is apparently balanced by telomere elongation6–10, which may involve de novo synthesis of additional repeats by a novel DNA… Expand
Telomere shortening in renal cell carcinoma.
TLDR
The data suggest that telomerase activation might occur in human renal cell carcinoma, and no correlation between tumor size and calculated tumor cell divisions undergone was found. Expand
The roles of telomeres and telomerase in cell life span.
TLDR
In humans and possibly other higher eukaryotes, telomere shortening may have been adopted to limit the life span of somatic cells, and can be countered by the de novo addition of telomeric repeats by the enzyme telomerase. Expand
Targeting telomeres and telomerase.
TLDR
It was proposed that telomerase-competent stern cells may regulateTelomerase activity to maintain levels sufficient to slow but not prevent telomere shortening, to produce even greater detrimental effects on cancer cell viability. Expand
Normal human chromosomes have long G-rich telomeric overhangs at one end.
TLDR
It is shown that following replication the daughter telomeres have different terminal overhangs in normal diploid telomerase-negative human fibroblasts, and variations in lagging-strand synthesis may regulate the rate of telomere shortening in normaldiploid human cells. Expand
Regulation of Telomere Length in Mammalian Cells
The ends of linear mammalian chromosomes consist of a simple repeated sequence (T2AG3)n [reviewed in 1,2]. These terminal repeats play a role in prevention of end to end fusion and prot7ection fromExpand
Mechanisms of telomere loss and their consequences for chromosome instability
TLDR
Understanding the mechanisms of telomere loss will provide important insights into both human cancer and genetic disease. Expand
Changes in telomerase activity and telomere length during human T lymphocyte senescence.
TLDR
The level of telomerase activity in activated peripheral blood T cells, the CTL cell line, and two leukemia cell lines does not correlate with the average TRF length, suggesting that other factors besides telomersase activity are involved in the regulation of telomere length. Expand
Telomere length regulation during cloning, embryogenesis and ageing.
TLDR
Early embryonic telomere elongation is telomerase dependent and leads to a rejuvenation of telomeres in cloned bovine embryos, which is of great interest for medical research in the fields of regeneration, cell therapies and therapeutic cloning. Expand
Models of initiation of replicative senescence by loss of telomeric DNA
  • R. Allsopp
  • Medicine, Biology
  • Experimental Gerontology
  • 1996
TLDR
This work favors a model in which replicative senescence is caused by the shortening of telomeres below a length that is critical for the maintenance of proper telomere structure and function. Expand
Reconstitution of telomerase activity in normal human cells leads to elongation of telomeres and extended replicative life span
TLDR
Results show that retroviral-mediated expression of hTERT resulted in functional telomerase activity in normal aging human cells, indicating that telomere length is one factor that can determine the replicative life span of human cells. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 30 REFERENCES
DNA sequences of telomeres maintained in yeast
TLDR
Yeast chromosomal telomeres terminate in a DNA sequence consisting of tandem irregular repeats of the general form C1–3A, in an apparently non-template-directed manner, during their replication on linear plasmids in yeast. Expand
Cloning of human telomeres by complementation in yeast
TLDR
A modified yeast artificial chromosome (YAC) vector with only one telomere is described which was used to clone human telomeres by complementation in yeast. Expand
Generation of telomere-length heterogeneity in Saccharomyces cerevisiae.
  • J. Shampay, E. Blackburn
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1988
TLDR
In vivo phenomena suggest that lengthening and shortening activities act on yeast telomeres during each round of replication, distinct from genetic regulation of chromosome length, which acts on all chromosome ends coordinately. Expand
Characterization of two telomeric DNA processing reactions in Saccharomyces cerevisiae.
TLDR
The elongation reaction was very efficient, and it is believed that it was responsible for maintaining an average telomere length despite incomplete replication by template-directed DNA polymerase. Expand
Structure and variability of human chromosome ends.
TLDR
A direct cloning strategy for telomere-associated DNA was developed based on the relative lack of restriction endonuclease cutting sites near the ends of human chromosomes, indicating that somatic telomeres are unstable and may continuously lose sequences from their termini. Expand
The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesizes TTAGGG repeats
TLDR
The identification of telomerase in HeLa cells with only approximately 100 telomeres indicates that telomersase-mediated telomere maintenance is conserved throughout eukaryotes. Expand
Identification of a specific telomere terminal transferase activity in tetrahymena extracts
TLDR
It is proposed that the novel telomere terminal transferase is involved in the addition of telomeric repeats necessary for the replication of chromosome ends in eukaryotes. Expand
Dynamics of telomere length variation in tetrahymena thermophila
TLDR
The demonstration that telomeres are dynamic structures provides evidence for a model of telomere length regulation by activities that add and remove telomeric repeats. Expand
Human telomeres contain at least three types of G-rich repeat distributed non-randomly.
TLDR
It is demonstrated here that human telomeres do not contain a pure uniform 6 base pair repeat unit but that there are at least three types of repeat, which are present at the ends of most or all human chromosomes. Expand
Loss of repetitious DNA in proliferating somatic cells may be due to unequal recombination.
TLDR
The estimated value of x is adequate to account for the rapid evolution of tandem arrays of repetitious DNA by unequal recombination, and cannot rule out active deletion of this component of the genome in human somatic cells by excision or incomplete replication. Expand
...
1
2
3
...