In human non-cancerous cells, the tips of chromosomes (called telomeres) progressively shorten each time a cell divides until they reach a critically short length that triggers the cell to stop cell division. Nearly all cancer cells evade this mechanism by activating an enzyme, named telomerase, which counteracts the shortening of chromosome ends and allows them to divide indefinitely. Telomerase inhibitors are highly efficient at inducing cell death in cancer cells in culture and in animal models, however, the current challenge of telomerase inhibition therapy is a long lag period between initiation of treatment and induction of cancer cell death. The ultimate goals of this proposal are to employ new assays to investigate how telomere structures are regulated throughout the cell cycle in normal and cancer cells and to correlate the effect of long-term telomerase inhibition and telomere structure with the induction of cancer cell death. ? ? ?
