21 DNA Telomerases

Telomerase is a specialized DNA polymerase that synthesizes telomeric DNA sequences onto chromosome ends. Linear DNA genomes pose a special problem for the DNA replication machinery. Because DNA polymerases function in the 5 to 3 direction and require a primer, part of the lagging strand is predicted to be lost at each round of division. For most eukaryotic chromosomes, sequence loss is balanced by the de novo addition of telomeric sequence by telomerase (for review, see Blackburn 1991). Telomere DNA sequences in ciliates consist of simple GT-rich tandem repeats, and this motif is generally conserved in eukaryotes, although the exact repeat sequence is species-specific. For example, Tetrahymena contains tandem TTGGGG repeats, whereas mammals have TTAGGG repeats (for review, see Blackburn 1991; Henderson 1995). Telomerase synthesizes these short repeats by using an integral RNA component of the enzyme as a template (Fig. 1) (Greider and Blackburn 1989). Telomerase activity has been identified from Tetrahymena, Euplotes, Oxytricha, yeast, Xenopus, and mammals. In each case, the sequence synthesized by telomerase in vitro corresponds to the telomere sequence of the organism from which it was isolated (Table l ) , and the RNA template contains more than one repeat of the sequence (Table 2) (Greider and Blackburn 1985; Zahler and Prescott 1988; Morin 1989; Shippen-Lentz and Blackburn 1989; Prowse et al. 1993; Lingner et al. 1994; Mantel1 and Greider 1994; Cohn and Blackburn 1995; Lin and Zakian 1995; Lue and Wang 1995).