title: Human telomerase contains evolutionarily conserved catalytic and structural subunits.
abstract: We have cloned and characterized a human gene encoding TP2 (telomerase-associated protein 2), a protein with similarity to reverse transcriptases and the catalytic telomerase subunits from Saccharomyces cerevisiae and Euplotes aediculatus. Indirect immunofluorescence revealed that TP2 was localized to the nucleus. Using antibodies to endogenous and epitope-tagged TP2, we found that TP2 was associated specifically with human telomerase activity and the recently identified telomerase-associated protein TP1. Mutation of conserved residues within the reverse transcriptase domain of TP2 severely reduced associated telomerase activity. These results suggest that telomerase is an evolutionarily conserved multisubunit complex composed of both structural and catalytic subunits.
authors.affiliation: Amgen Institute/Ontario Cancer Institute, Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2C1, Canada. Leah@amgen.com
authors.forename: L
authors.initials: L
authors.lastname: Harrington
authors.forename: W
authors.initials: W
authors.lastname: Zhou
authors.forename: T
authors.initials: T
authors.lastname: McPhail
authors.forename: R
authors.initials: R
authors.lastname: Oulton
authors.forename: D S
authors.initials: DS
authors.lastname: Yeung
authors.forename: V
authors.initials: V
authors.lastname: Mar
authors.forename: M B
authors.initials: MB
authors.lastname: Bass
authors.forename: M O
authors.initials: MO
authors.lastname: Robinson
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002384:Catalysis; D002467:Cell Nucleus / Q000378:metabolism; D017124:Conserved Sequence; D004268:DNA-Binding Proteins; D019143:Evolution, Molecular; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012313:RNA; D016601:RNA-Binding Proteins; D012194:RNA-Directed DNA Polymerase / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D019098:Telomerase / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; C104342:TEP1 protein, human; C422952:telomerase RNA; D012313:RNA; D012194:RNA-Directed DNA Polymerase; D019098:Telomerase