Cellular Aging: Telomeres
Telomeres, Genome Stability, And Cancer
The hallmark of telomeres is their ability to confer stability on chromosome ends and prevent chromosome ends from activating the cellular surveillance mechanisms protecting cells from the deleterious effects of DNA breaks. Chromosomes with critically short telomeres become compromised in chromosome-end stability, and, because telomeres are generally shorter in tumors than in adjacent healthy tissue, it was suggested that telomere dysfunction could contribute to tumorigenesis by increasing genomic instability. In the short term, this genomic instability might promote tumor formation by allowing growth-advantageous mutations (i.e., mutations that permit cells to remain viable under conditions when, normally, the cells would die) to accumulate rapidly. However, this scenario requires that the cellular mechanism(s) that normally monitor telomere length and prevent cells with critically short telomeres from dividing be blocked. Under these conditions, cells with critically short telomeres would continue dividing. These cells would enter a period of extreme chromosomal instability. Eventually, however, such rampant genome instability might prove deleterious to tumor survival by generating mutations in genes that are essential for cellular survival. Thus, stabilization of the genome, perhaps through activation of telomerase, would have a selective advantage. Experiments carried out by the DePinho and Greider groups utilizing telomerase-deficient mice support the idea that transient telomere malfunction may promote tumorigenesis.
- Cellular Aging: Telomeres - Telomeres, Aging, And Cancer
- Cellular Aging: Telomeres - Telomeres As Tumor Suppressors
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