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(-/-) 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 manner. This telomere-maintenance in the absence of telomerase could provide the basis for the ability of mTER(-/-) cells to grow indefinitely and form tumors.
CITATION STYLE
Hande, M. P., Samper, E., Lansdorp, P., & Blasco, M. A. (1999). Telomere length dynamics and chromosomal instability in cells derived from telomerase null mice. Journal of Cell Biology, 144(4), 589–601. https://doi.org/10.1083/jcb.144.4.589
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