Abstract
Aberrant activation of telomerase occurs in 85–90% of all cancers and underpins the ability of cancer cells to bypass their proliferative limit, rendering them immortal. The activity of telomerase is tightly controlled at multiple levels, from transcriptional regulation of the telomerase components to holoenzyme biogenesis and recruitment to the telomere, and finally activation and processivity. However, studies using cancer cell lines and other model systems have begun to reveal features of telomeres and telomerase that are unique to cancer. This review summarizes our current knowledge on the mechanisms of telomerase recruitment and activation using insights from studies in mammals and budding and fission yeasts. Finally, we discuss the differences in telomere homeostasis between normal cells and cancer cells, which may provide a foundation for telomere/telomerase targeted cancer treatments.
Highlights
Aberrant activation of telomerase occurs in 85 –90% of all cancers and underpins the ability of cancer cells to bypass their proliferative limit, rendering them immortal
This review summarizes our current knowledge on the mechanisms of telomerase recruitment and activation using insights from studies in mammals and budding and fission yeasts
We summarize our current knowledge of fundamental telomerase action, and highlight the phenotypes uniquely observed in cancer cells
Summary
All dividing eukaryotic cells require telomeres to maintain the ends of the chromosomes and sustain chromosome stability. Most somatic cells that have undergone sufficient cell divisions to cause critical telomere shortening enter into replicative senescence. A direct correlation between telomere maintenance and indefinite cell division was demonstrated in vitro by ectopic expression of telomerase in somatic cell culture [11]. Some of them are critically short, termed ‘t-stumps’ [14], resulting in immortal cells that sustain a high risk of chromosome instability. This is strikingly different from our understanding of telomerase action in normal cells, in which telomerase preferentially elongates shorter telomeres until they are no longer short [15,16,17]. We summarize our current knowledge of fundamental telomerase action, and highlight the phenotypes uniquely observed in cancer cells
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