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Vol. 11, No. 21,
pp. 2801-2809,
November 1, 1997
1 Department of Cell Biology and Neuroscience, The University of Texas Southwestern Medical Center, Dallas, Texas 75235-9039 USA; 2 Program in Molecular and Cell Biology, University of Texas at Dallas, Richardson, Texas 75083 USA
Telomeres protect the ends of linear chromosomes from degradation
and abnormal recombination events, and in vertebrates may be important
in cellular senescence and cancer. However, very little is known about
the structure of human telomeres. In this report we purify telomeres
and analyze their termini. We show that following replication the
daughter telomeres have different terminal overhangs in normal diploid
telomerase-negative human fibroblasts. Electron microscopy of those
telomeres that have long overhangs yields 200 ± 75 nucleotides of
single-stranded DNA. This overhang is four times greater than the
amount of telomere shortening per division found in these cells. These
results are consistent with models of telomere replication in which
leading-strand synthesis generates a blunt end while lagging-strand
synthesis produces a long G-rich 3
overhang, and suggest that
variations in lagging-strand synthesis may regulate the rate of
telomere shortening in normal diploid human cells. Our results do not
exclude the possibility that nuclease processing events following
leading strand synthesis result in short overhangs on one end.
[Key Words: Telomeres; DNA replication; chromosome structure; cellular senescence; aging]
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