Fundamental mechanisms of telomerase action in yeasts and mammals: understanding telomeres and telomerase in cancer cells.
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.
Chromosome Maintenance Group, UCL Cancer Institute, University College London, 72 Huntley Street, London WC1E 6DD, UK.
Christine A
CA
Armstrong
Chromosome Maintenance Group, UCL Cancer Institute, University College London, 72 Huntley Street, London WC1E 6DD, UK k.tomita@ucl.ac.uk.
Kazunori
0000-0003-1096-6725
K
Tomita
D000818:Animals; D049109:Cell Proliferation; D004789:Enzyme Activation; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D004718:Saccharomycetales / Q000737:chemistry / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000737:chemistry / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D019098:Telomerase / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D059505:Telomere Homeostasis; D015533:Transcriptional Activation
D019098:Telomerase
Hayflick limit; S. pombe; replicative senescence; shelterin; t-stumps; telomere length homeostasis