Abstract
In recent years, Hsp90 is found to interact with several telomeric proteins at various phases of cell cycle. The Hsp90 chaperone system controls assembly and disassembly of telomere structures and thus maintains the dynamic state of telomere. Here, for the first time we report that the activity of another telomeric protein Sir2p is modulated by Hsp82, the ortholog of Hsp90 from budding yeast (Saccharomyces cerevisiae). In a temperature sensitive Hsp90 deficient yeast strain (iG170Dhsp82), less abundant Sir2p is observed, resulting in de-repression of telomere silencing and a complete loss of mating type silencing. Intriguingly, over expression of Hsp90, either by exposing cells to heat shock or by introducing HSP82 overexpression plasmid also yields reduced level of Sir2p, with a consequential loss of telomere silencing. Thus, Hsp90 homeostasis maintains the cellular pool of Sir2p and thereby controls the reversible nature of telomere silencing. Interestingly, such regulation is independent of one of its major co-chaperones Sba1 (human ortholog of p23).
Highlights
Hsp90 is a highly abundant eukaryotic protein, which is involved in maturation and folding of some special class of proteins, which are primarily involved in signal transduction [1,2,3]
To explore whether Sir2p function is dependent on Hsp82, we examined both the mating type silencing as well as telomere position effect in a conditional mutant, where Hsp82 is functionally defective
We observe that in iGD170hsp82 temperature sensitive mutant, where Hsp82 is nonfunctional at restrictive temperature, there is significant reduction of Sir2p which is associated with loss of mating type silencing as well transcriptional silencing at telomere
Summary
Hsp is a highly abundant eukaryotic protein, which is involved in maturation and folding of some special class of proteins, which are primarily involved in signal transduction [1,2,3] It dimerises in an ATP dependent manner with several cochaperones and provides the maturation of the target protein at a near native state [4]. Examples include Cdc, Stn1, [14,15], Sir2 [16], Mre11 [17], Ku80, Mec and Est1 [15] Some of these gene products are involved in telomere position effect (TPE) [18], a phenomenon where transcription of gene is repressed by its close proximity to telomere
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