Telomeres, telomerase, and tumorigenesis--a review

Human telomeres function as a protective structure capping both ends of the chromosome. They are composed of long, repetitive sequences of TTAGGG, associated with a variety of telomere-binding proteins. Telomeres protect the chromosomes from end-to-end fusion, recombination, and degradation, all events that can lead to cell death. At cell replication, telomeres cannot be completely replicated. They are gradually shortened, and when the telomeres reach a critical threshold, cell replication is arrested in what is called "replicative senescence." Thus, telomeres act as an intrinsic "counting" mechanism of the cell's aging process. Telomerase is an enzymatic ribonucleoprotein complex that acts as a reverse transcriptase in the elongation of telomeres. Telomerase activity is almost absent in somatic cells, but it is detected in embryonic stem cells and in the vast majority of tumor cells. Tumor cells, in fact, may contain short and stable telomeres that confer immortality to the cancer cells, which are thus able to replicate indefinitely. The deregulation of telomeres thus plays an important role in the relationship between premature aging syndrome and cancer. This review describes the recent advances in the molecular characterization of telomeres, the regulation of telomerase