|
||
J. Cell Biol.,
Volume 144, Number 4, February 22, 1999 589-601

§
* Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Campus Cantoblanco, Madrid
E-28049, Spain; To study the effect of continued telomere
shortening on chromosome stability, we have analyzed
the telomere length of two individual chromosomes
(chromosomes 2 and 11) in fibroblasts derived from
wild-type mice and from mice lacking the mouse telomerase RNA (mTER) gene using quantitative fluorescence in situ hybridization. Telomere length at both
chromosomes decreased with increasing generations of
mTER
Terry Fox Laboratory, British Columbia Cancer Research Center, Vancouver, British Columbia V5Z 1L3,
Canada; and § Department of Medicine, University of British Columbia, Vancouver, British Columbia V6T 2B5, Canada
/
mice. At the 6th mouse generation, this telomere shortening resulted in significantly shorter chromosome 2 telomeres than the average telomere length
of all chromosomes. Interestingly, the most frequent fusions found in mTER
/
cells were homologous fusions
involving chromosome 2. Immortal cultures derived
from the primary mTER
/
cells showed a dramatic accumulation of fusions and translocations, revealing that
continued growth in the absence of telomerase is a potent inducer of chromosomal instability. Chromosomes
2 and 11 were frequently involved in these abnormalities suggesting that, in the absence of telomerase, chromosomal instability is determined in part by chromosome-specific telomere length. At various points during
the growth of the immortal mTER
/
cells, telomere
length was stabilized in a chromosome-specific man-ner. This telomere-maintenance in the absence of
telomerase could provide the basis for the ability of
mTER
/
cells to grow indefinitely and form tumors.
This article has been cited by other articles:
|
|