Fig. 1.

Unique nucleic acid handling specificities adapt telomerase for repeat synthesis. (A) The telomerase catalytic cycle begins with formation of the initial primer–template duplex, which docks in the active site for repeat synthesis. Step 2 is proposed to be rate limiting by refs. 5 and 7, and steps 4–7 and 1 could be in reversible equilibrium (7). Step 3 has been shown to be duplex sequence dependent (5). After repeat completion, duplex is proposed to release from the active site (step 4a). We suggest this release could be mediated through single-stranded DNA filling of a nascent product binding site, with or without sliding of remaining duplex from the active site (step 4b). (B) A template-adjacent RNA stem (i) and duplex sequence-based signal (ii) define the boundaries of the region of TER used as template.