Telomeres, telomerase, and apoptosis.
Telomeres are specialized high-order chromatin structures that cap the ends of eukaryotic chromosomes. In vertebrates, telomeric DNA is composed of repetitions of the TTAGGG hexanucleotide, is bound to a set of specific proteins, and is elongated by the reverse transcriptase enzyme telomerase. Telomerase activity is promptly detected in cells with an indefinite replicative potential, such as cancer cells, while is almost undetectable in normal cells, which are characterized by a limited life span. Mounting evidence indicates that the maintenance of telomere integrity and telomerase protect cells from apoptosis. Disruption of the telomere capping function and (or) telomerase inhibition elicit an apoptotic response in cancer cells, while restoration of telomerase activity in somatic cells confers resistance to apoptosis. The possible mechanisms linking telomeres, telomerase and apoptosis are discussed in this review, together with the impact of this field in anticancer research.
Istituto di Genetica Molecolare CNR, Pavia, Italy.
Chiara
C
Mondello
A Ivana
AI
Scovassi
D000818:Animals; D017209:Apoptosis; D002843:Chromatin / Q000502:physiology; D004247:DNA / Q000737:chemistry; D004268:DNA-Binding Proteins; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009369:Neoplasms / Q000473:pathology; D009711:Nucleotides / Q000737:chemistry; D019098:Telomerase / Q000235:genetics / Q000502:physiology*; D016615:Telomere / Q000648:ultrastructure*
D002843:Chromatin; D004268:DNA-Binding Proteins; D009711:Nucleotides; D004247:DNA; D019098:Telomerase