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Coordinated DNA dynamics during the human telomerase catalytic cycle.

Authors
Type
Published Article
Journal
Nature Communications
Publisher
Springer Nature
Volume
5
Pages
4146–4146
Identifiers
DOI: 10.1038/ncomms5146
Source
UCSC Aging biomedical-ucsc
License
Unknown

Abstract

The human telomerase reverse transcriptase (hTERT) utilizes a template within the integral RNA subunit (hTR) to direct extension of telomeres. Telomerase exhibits repeat addition processivity (RAP) and must therefore translocate the nascent DNA product into a new RNA:DNA hybrid register to prime each round of telomere repeat synthesis. Here, we use single-molecule FRET and nuclease protection assays to monitor telomere DNA structure and dynamics during the telomerase catalytic cycle. DNA translocation during RAP proceeds through a previously uncharacterized kinetic substep during which the 3 -end of the DNA substrate base pairs downstream within the hTR template. The rate constant for DNA primer realignment reveals this step is not rate limiting for RAP, suggesting a second slow conformational change repositions the RNA:DNA hybrid into the telomerase active site and drives the extrusion of the 5 -end of the DNA primer out of the enzyme complex.

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