Telomerase Holoenzyme Assembly

Abstract

Maintenance of the terminal telomeric repeat tracts requires new repeat synthesis by the specialized ribonucleoprotein reverse transcriptase telomerase. Reconstitution of telomerase enzyme activity in vitro requires the template‐containing telomerase RNA subunit (TER) and the telomerase reverse transcriptase protein (TERT). Numerous additional subunits coassemble or interact with the endogenously functional telomerase holoenzyme complex. Recent studies in the Collins laboratory have focused on defining the factors required for assembly and activity of telomerase holoenzyme using two model systems: the single‐celled ciliated protozoan Tetrahymena and cultured human cells. We have begun to elucidate the biochemical mechanisms that underlie unique features of the telomerase catalytic cycle such as the use of an internal RNA template and the processive synthesis of single‐stranded DNA repeats.