Telomeres shorten during ageing of human fibroblasts.

Nature 1990 May;345(6274):458-60

Department of Biochemistry, McMaster University, Hamilton, Ontario, Canada.

The terminus of a DNA helix has been called its Achilles' heel. Thus to prevent possible incomplete replication and instability of the termini of linear DNA, eukaryotic chromosomes end in characteristic repetitive DNA sequences within specialized structures called telomeres. In immortal cells, loss of telomeric DNA due to degradation or incomplete replication is apparently balanced by telomere elongation, which may involve de novo synthesis of additional repeats by novel DNA polymerase called telomerase. Such a polymerase has been recently detected in HeLa cells. It has been proposed that the finite doubling capacity of normal mammalian cells is due to a loss of telomeric DNA and eventual deletion of essential sequences. In yeast, the est1 mutation causes gradual loss of telomeric DNA and eventual cell death mimicking senescence in higher eukaryotic cells. Here, we show that the amount and length of telomeric DNA in human fibroblasts does in fact decrease as a function of serial passage during ageing in vitro and possibly in vivo. It is not known whether this loss of DNA has a causal role in senescence.

Download full-text PDF

Source
http://dx.doi.org/10.1038/345458a0DOI Listing
May 1990
136 Reads

Publication Analysis

Top Keywords

telomeric dna
16
loss telomeric
12
dna
9
incomplete replication
8
human fibroblasts
8
cells loss
8
dna eventual
8
finite doubling
4
proposed finite
4
hela cells
4
doubling capacity
4
cells proposed
4
capacity normal
4
detected hela
4
normal mammalian
4
eventual deletion
4
mammalian cells
4
deletion essential
4
polymerase called
4
involve novo
4

References

(Supplied by CrossRef)

AM Olovnikov et al.
J. theor. Biol. 1973

JD Watson et al.
Nature new Biol. 1972

HJ Mueller et al.
Collecting Net 1938

B McClintock et al.
Genetics 1941

EH Blackburn et al.
A. Rev. Biochem. 1984

A Bernards et al.
Nature 1983

J Shampay et al.
Nature 1984

DD Larson et al.
Cell 1987

J Shampay et al.
Proc. natn. Acad. Sci. U.S.A. 1988

AW Murray et al.
Molec. cell. Biol. 1988

CW Greider et al.
Nature 1989

Similar Publications