title: The hsp90 molecular chaperone modulates multiple telomerase activities.
abstract: 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.
authors.affiliation: Department of Cell and Developmental Biology, University of Illinois, Urbana-Champaign, 601 S. Goodwin Avenue, Urbana, IL 61801, USA.
authors.forename: Oyetunji A
authors.initials: OA
authors.lastname: Toogun
authors.forename: Diane C
authors.initials: DC
authors.lastname: Dezwaan
authors.forename: Brian C
authors.initials: BC
authors.lastname: Freeman
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D004271:DNA, Fungal / Q000096:biosynthesis; D005998:Glycine / Q000235:genetics / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*
chemical_list: D004271:DNA, Fungal; C074510:HSP82 protein, S cerevisiae; D018841:HSP90 Heat-Shock Proteins; D029701:Saccharomyces cerevisiae Proteins; D019098:Telomerase; D000251:Adenosine Triphosphatases; D005998:Glycine