An RPA-related sequence-specific DNA-binding subunit of telomerase holoenzyme is required for elongation processivity and telomere maintenance.

Telomerase ribonucleoprotein complexes copy an internal RNA template to synthesize DNA repeats. DNA-interacting subunits other than telomerase reverse transcriptase (TERT) and telomerase RNA (TER) have been hypothesized to account for high repeat addition processivity of telomerase holoenzyme compared to the minimal catalytic RNP. Here, we present the identification of three additional subunits of Tetrahymena thermophila telomerase holoenzyme. Each of seven telomerase proteins is required for telomere maintenance and copurifies active RNP. The catalytic core (p65-TER-TERT) is assembled with a three-protein subcomplex (p75-p45-p19) and two peripheral subunits (p82 and p50). Remarkably, only a p82-enriched subset of the total holoenzyme population is capable of high repeat addition processivity, as shown by p82 immunodepletion and add-back. The RPA-like p82 subunit binds sequence specifically to multiple telomeric repeats. These discoveries establish the existence of a telomerase holoenzyme processivity subunit with sequence-specific DNA binding.