Telomeres and telomerase: Implications for cancer and aging

Maintenance of telomere stability is required for cells to escape from repl icative senescence and proliferate indefinitely. Telomere length is maintai ned by a balance between processes that lengthen telomeres (telomerase) and processes that shorten telomeres (the end-replication problem). Telomerase is a cellular ribonucleoprotein reverse transcriptase which stabilizes tel omere length by adding hexameric (TTAGGG) repeats to the telomeric ends of the chromosomes, thus compensating for the continued erosion of telomeres, Introduction of the telomerase catalytic protein component into normal telo merase-negative human cells results in restoration of telomerase activity a nd extension of cellular life span, Human cells with introduced telomerase maintain a normal chromosome complement and continue to grow in a normal ma nner. Telomerase-induced manipulations of telomere length may thus be impor tant not only for cell and tissue engineering but also for dissecting the m olecular mechanisms underlying inherited genetic diseases, as well as defin ing the genetic pathways leading to cancer, Because almost all human tumors express telomerase activity, inhibition of telomerase may result in gradua l erosion of telomeres and eventual cessation of cell proliferation or indu ction of apoptosis, Thus telomerase may also be a promising target for canc er therapy. (C) 2001 by Radiation Research Society.