Role of telomerase in cell senescence and oncogenesis

The ends of linear chromosomes are capped by specialized nucleoprotein stru ctures termed telomeres. Telomeres comprise tracts of noncoding hexanucleot ide repeat sequences that, in combination with specific proteins, protect a gainst degradation, rearrangement, and chromosomal fusion events. Due to th e polarity of conventional DNA synthesis, a net loss of telomeric sequences occurs at each cell division. It has been proposed that this cumulative te lomeric erosion is a limiting factor in replicative capacity and elicits a signal for the onset of cellular senescence. To proliferate beyond the sene scent checkpoint, cells must restore telomere length. This can be achieved by telomerase, an enzyme with reverse-transcriptase activity. This enzyme i s absent in differentiated somatic tissues, but telomerase reactivation has been detected in most tumors. Much investigative effort is focusing on tel omere dynamics with a view to possible manipulation of cellular proliferati ve potential. In this article, we review the role of telomeres and telomera se in senescence and tumor progression, and we discuss the potential use of telomerase in diagnosis and treatment.