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Vol. 11, Issue 10, 3329-3340, October 2000
and
*Ontario Cancer Institute/Amgen Institute, Department of Medical
Biophysics, University of Toronto, Toronto, Ontario M5G 2C1 Canada; and
The minimal, active core of human telomerase is postulated to
contain two components, the telomerase RNA hTER and the telomerase reverse transcriptase hTERT. The reconstitution of human telomerase activity in vitro has facilitated the identification of sequences within the telomerase RNA and the RT motifs of hTERT that are essential
for telomerase activity. However, the precise role of residues outside
the RT domain of hTERT is unknown. Here we have delineated several
regions within hTERT that are important for telomerase catalysis,
primer use, and interaction with the telomerase RNA and the
telomerase-associated protein TEP1. In particular, certain deletions of
the amino and carboxy terminus of hTERT that retained an interaction
with telomerase RNA and TEP1 were nonetheless completely inactive in
vitro and in vivo. Furthermore, hTERT truncations lacking the amino
terminus that were competent to bind the telomerase RNA were severely
compromised for the ability to elongate telomeric and nontelomeric
primers. These results suggest that the interaction of telomerase RNA
with hTERT can be functionally uncoupled from polymerization, and that
there are regions outside the RT domain of hTERT that are critical for
telomerase activity and primer use. These results establish that the
human telomerase RT possesses unique polymerization determinants that
distinguish it from other RTs.
Amgen Inc., Thousand Oaks, California 91320
Corresponding author: E-mail address:
leah{at}oci.utoronto.ca.
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