HUMAN TELOMERASE CONTAINS EVOLUTIONARILY CONSERVED CATALYTIC AND STRUCTURAL SUBUNITS

We have cloned and characterized a human gene encoding TP2 (telomerase -associated protein 2), a protein with similarity to reverse transcrip tases and the catalytic telomerase subunits from Saccharomyces cerevis iae and Euplotes aediculatus. Indirect immunofluorescence revealed tha t TP2 was localized to the nucleus. Using antibodies to endogenous and epitope-tagged TP2, we found that TP2 was associated specifically wit h human telomerase activity and the recently identified telomerase-ass ociated protein TP1. Mutation of conserved residues within the reverse transcriptase domain of TP2 severely reduced associated telomerase ac tivity. These results suggest that telomerase is an evolutionarily con served multisubunit complex composed of both structural and catalytic subunits.