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Mol. Cell. Biol. doi:10.1128/MCB.02368-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Characterization of Physical and Functional Anchor Site Interactions in Human Telomerase

Southern Alberta Cancer Research Institute and Department of Biochemistry and Molecular Biology, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada, T2N 4N1

^* To whom correspondence should be addressed. Email: tbeattie{at}ucalgary.ca.

	Abstract

Telomerase is a ribonucleoprotein reverse transcriptase that processively synthesizes telomeric repeats onto the ends of linear chromosomes to maintain genomic stability. It has been proposed that the N-terminus of the telomerase protein subunit, TERT, contains an anchor site that forms stable interactions with DNA to prevent enzyme/DNA dissociation during translocation and to promote re-alignment events that accompany each round of telomere synthesis. However, it has not yet been established if the human telomerase reverse transcriptase (hTERT) can directly interact with DNA in the absence of the telomerase RNA subunit. Here we use a novel primer binding assay to establish that hTERT forms stable and specific interactions with telomeric DNA in the absence of the human telomerase RNA component, hTR. We show that hTERT-mediated primer binding can be functionally uncoupled from telomerase-mediated primer extension. Our results demonstrate that the first 350 amino acids of hTERT have a critical role in regulating the strength and specificity of protein-DNA interactions, providing additional evidence that the TERT N-terminus contains an anchor site. Furthermore, we establish that the hTERT RT domain mediates important protein-DNA interactions. Collectively, these data suggest that hTERT contains distinct anchor regions that co-operate to help regulate telomerase-mediated DNA recognition and elongation.

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