THE ROLES OF TELOMERES AND TELOMERASE IN CELL LIFE-SPAN

Telomeres cap and protect the ends of chromosomes from degradation and illegitimate recombination. The termini of a linear template cannot, however, be completely replicated by conventional DNA-dependent DNA po lymerases, and thus in the absence of a mechanisms to counter this eff ect, telomeres of eukaryotic cells shorten every round of DNA replicat ion. In humans and possibly other higher eukaryotes, telomere shorteni ng may have been adopted to limit the life span of somatic cells. Huma n somatic cells have a finite proliferative capacity and enter a viabl e growth arrested state called senescence. Life span appears to be gov erned by cell division, not time. The regular loss of telomeric DNA co uld therefore serve as a mitotic clock in the senescence programme, co unting cell divisions. In most eukaryotic organisms, however, telomere shortening can be countered by the de novo addition of telomeric repe ats by the enzyme telomerase. Cells which are 'immortal' such as the h uman germ line or tumour cell lines, established mouse cells, yeast an d ciliates, all maintain a stable telomere length through the action o f telomerase. Abolition of telomerase activity in such cells neverthel ess results in telomere shortening, a process that eventually destabil izes the ends of chromosomes, leading to genomic instability and cell growth arrest or death. Therefore, loss of terminal DNA sequences may limit cell life span by two mechanisms: by acting as a mitotic clock a nd by denuding chromosomes of protective telomeric DNA necessary for c ell viability.