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Molecular and Cellular Biology, January 2008, p. 457-467, Vol. 28, No. 1
0270-7306/08/$08.00+0     doi:10.1128/MCB.01417-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

The Hsp90 Molecular Chaperone Modulates Multiple Telomerase Activities{triangledown}

Oyetunji A. Toogun ,{dagger},{ddagger} Diane C. DeZwaan,{dagger} and Brian C. Freeman*

Department of Cell and Developmental Biology, University of Illinois, Urbana-Champaign, 601 S. Goodwin Avenue, Urbana, Illinois 61801

Received 7 August 2007/ Returned for modification 29 August 2007/ Accepted 8 October 2007

The Hsp90 molecular chaperone is a highly abundant eukaryotic molecular chaperone. While it is understood that Hsp90 modulates a significant number of proteins, the mechanistic contributions made by Hsp90 to a client protein typically are not well understood. Here we investigate the yeast Hsp90 regulatory roles with telomerase. Telomerase lengthens chromosome termini by specifically associating with single-stranded telomeric DNA and appending nucleotides by reverse transcription. We have found that the yeast Hsp90 homolog Hsp82p promotes both telomerase DNA binding and nucleotide addition properties. By isolating telomerase from different allelic backgrounds we observed distinct defects. For example, in an hsp82 T101I strain telomerase displayed decreased nucleotide processivity, whereas both DNA binding and extension activities were lowered in a G170D background. The decline in telomerase DNA binding correlated with a loss of Hsp82p association. No matter the defect, telomerase activity was recovered upon Hsp82p addition. Importantly, telomere length and telomerase telomere occupancy was yeast Hsp90 dependent. Taken together, our results indicate that Hsp82p promotes telomerase DNA association and facilitates DNA extension once telomerase is engaged with the DNA.


* Corresponding author. Mailing address: Department of Cell and Developmental Biology, University of Illinois, Urbana-Champaign, 601 S. Goodwin Avenue, Urbana, IL 61801. Phone: (217) 244-2662. Fax: (217) 244-1648. E-mail: bfree{at}uiuc.edu

{triangledown} Published ahead of print on 22 October 2007.

{dagger} O.A.T. and D.C.D. contributed equally to this study.

{ddagger} Deceased.


Molecular and Cellular Biology, January 2008, p. 457-467, Vol. 28, No. 1
0270-7306/08/$08.00+0     doi:10.1128/MCB.01417-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.




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