Nucleic Acids Research, Vol 26, Issue 6 1487-1494, Copyright © 1998 by Oxford University Press
NF Lue and Y Peng
A number of published studies indicate that telomerase may interact with
oligonucleotide primers in a bipartite manner, with the 3'-end of the
primer positioned at the catalytic site of the enzyme and a more 5' region
of the primer binding to a second or 'anchor' site of the enzyme. We
systematically investigated the effects of mutations in the DNA primer on
overall binding and polymerization by yeast telomerase. Our studies
indicate that there is sequence-specific interaction between telomerase and
a substantial region of the DNA primer. Mutations in the 3'-most positions
of the primer reduced polymerization, yet had little effect on overall
binding affinity. In contrast, mutations around the -20 position reduced
binding affinity but had no effect on polymerization. Most strikingly,
mutations centered around the -12 position of the DNA primer reduced
overall binding affinity but dramatically enhanced primer extension, as
well as primer cleavage. This finding suggests that reduced interaction
with the -12 region of the DNA primer can facilitate a step in the
catalytic region of yeast telomerase that leads to greater polymerization.
A tripartite model of interaction between primer and telomerase is proposed
to account for the distinct effects of mutations in different regions of
the DNA primer.
ARTICLES
Negative regulation of yeast telomerase activity through an interaction with an upstream region of the DNA primer
Department of Microbiology, W.R.Hearst Microbiology Research Center, Cornell University Medical College, 1300 York Avenue, New York, NY 10021, USA. nflue@mail.med.cornell.edu
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