Carcinogenesis, Vol 19, 259-265, Copyright © 1998 by Oxford University Press
JP Day, CL Limoli and WF Morgan
The physical termini of mammalian chromosomes are capped with tandem
repeats of the telomere sequence (TTAGGG)n. After fluorescence in situ
hybridization with a labeled (TTAGGG)n probe, telomere-repeat-like
sequences are seen as discrete bands at distinct intrachromosomal sites in
a variety of vertebrate species. There is increasing evidence that these
sites may be hot-spots for chromosomal rearrangements, fragility and
neoplasia. We have investigated whether the interstitial telomere bands
found in hamster chromosomes from a human hamster hybrid cell line are
hot-spots for chromosome rearrangements induced by DNA- damaging agents.
Our data indicate that the interstitial telomere bands are involved in
chromosomal rearrangements observed at the first mitosis after G1 exposure
of cells to X-rays or restriction endonucleases at a four- to fivefold
higher frequency than expected based on their size. In addition, we have
extended these observations to demonstrate for the first time that these
interstitial telomere- repeat-like sequences participate in the delayed
chromosomal instability observed in the progeny of cells surviving
X-ray-exposure at multiple generations after irradiation. In two highly
unstable clones showing multiple populations of rearranged chromosomes,
interstitial telomere bands were observed at the site of recombination
between the human and hamster chromosomes at a five- to sixfold higher
frequency than expected. There were also rearrangement and amplification of
the interstitial telomere bands within the hamster chromosomes. These
rearrangements occur during clonal expansion of cells surviving treatment
with DNA-damaging agents and suggest a role for the interstitial telomere
band in driving chromosomal instability. We conclude from the observed data
that interstitial telomere bands function as recombinational hot-spots that
participate in generating the diverse chromosome rearrangements observed
both immediately and as a delayed effect of cellular exposure to DNA
damaging agents.
ARTICLES
Recombination involving interstitial telomere repeat-like sequences promotes chromosomal instability in Chinese hamster cells
Department of Radiation Oncology, University of California, San Francisco 94143-0750, USA.
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