Telomeres and Telomerase: A Means to an End
Telomeres, consisting of simple repeated DNA sequences together with bound protein factors at the ends of chromosomes, make "caps" that protect and stabilize chromosomes. Without telomeric DNA and its special way of replicating, chromosome ends dwindle away as cells divide. Telomerase not only replenishes the DNA at telomeres, through its unique mechanism of internal RNA-templated addition of telomeric DNA, but also appears to provide other functions to protect the telomeres, thus counteracting cell senescence. Loss of telomere function and consequent cellular senescence may occur in human aging. Indeed, recent clinical and experimental observations indicate provocative links between telomerase and diseases of ageing such as heart disease.
Telomerase also plays key roles in cancer. Late-stage cancer cells characteristically have high telomerase levels. While the major known function of telomerase in cancer is to replenish telomeric DNA and maintain cell immortality, a rapid and distinct cellular/transcriptional response was elicited by reducing the level of telomerase ribonucleoprotein. This response occurred without any detectable telomere uncapping, shortening or DNA damage response. These and other recent results show that telomerase likely plays roles in other aspects of cancer known to be central to cancer progression. How this property of cancer cells can be exploited, with potential therapeutic applications, will be discussed.