18 Telomerases

Abstract

Telomeres, the specialized DNA-protein structures comprising the chromosomal termini in eukaryotes, are required to stabilize chromosomes and allow the complete replication of the 5′ ends of the chromosomal DNA (for review, see Blackburn and Szostak 1984; Zakian 1989; Blackburn 1991). Telomeres are the most conserved of the essential eukaryotic cis-acting chromosomal DNA elements with respect to both structure and function. This conservation may be a consequence of their unusual mode of synthesis. The sequence of telomeric DNA is specified by the enzyme telomerase (Greider and Blackburn 1985Greider and Blackburn 1987; Zahler and Prescott 1988; Morin 1989; Shippen-Lentz and Blackburn 1989). Telomerase is a ribonucleoprotein whose RNA and protein moieties are both essential for activity (Greider and Blackburn 1987). A sequence within the telomerase RNA is used as the template for synthesis of one telomeric strand (Greider and Blackburn 1989; Shippen-Lentz and Blackburn 1990). Furthermore, telomerase appears to be essential for telomere maintenance and hence for long-term viability of cells (for review, see Blackburn 1991). In this chapter, I describe this specialized reverse transcriptase.

Telomeric DNA consists of simple tandemly repeated sequences, characterized by clusters of G residues in one strand and an overall strand composition asymmetry, which results in a relatively G-rich versus C-rich strand. Table 1 shows the repeated sequence units of telomeric DNA in representative diverse eukaryotes. A given species has a characteristic telomeric repeat sequence common to the ends of all of its chromosomes. A terminal stretch of this simple-sequence DNA, typically a few hundred base pairs long in...