Cell division is essential for elimination of the yeast [PSI+] prion by guanidine hydrochloride.
Guanidine hydrochloride (Gdn.HCl) blocks the propagation of yeast prions by inhibiting Hsp104, a molecular chaperone that is absolutely required for yeast prion propagation. We had previously proposed that ongoing cell division is required for Gdn.HCl-induced loss of the [PSI+] prion. Subsequently, Wu et al.[Wu Y, Greene LE, Masison DC, Eisenberg E (2005) Proc Natl Acad Sci USA 102:12789-12794] claimed to show that Gdn.HCl can eliminate the [PSI+] prion from alpha-factor-arrested cells leading them to propose that in Gdn.HCl-treated cells the prion aggregates are degraded by an Hsp104-independent mechanism. Here we demonstrate that the results of Wu et al. can be explained by an unusually high rate of alpha-factor-induced cell death in the [PSI+] strain (780-1D) used in their studies. What appeared to be no growth in their experiments was actually no increase in total cell number in a dividing culture through a counterbalancing level of cell death. Using media-exchange experiments, we provide further support for our original proposal that elimination of the [PSI+] prion by Gdn.HCl requires ongoing cell division and that prions are not destroyed during or after the evident curing phase.
Byrne
Lee J
LJ
Protein Science Group, Department of Biosciences, University of Kent, Canterbury CT2 7NJ, United Kingdom.
Cox
Brian S
BS
Cole
Diana J
DJ
Ridout
Martin S
MS
Morgan
Byron J T
BJ
Tuite
Mick F
MF
D002455:Cell Division / Q000502:physiology*; D019791:Guanidine / Q000494:pharmacology*; D000072235:Mating Factor; D008954:Models, Biological; D010455:Peptides / Q000502:physiology; D011328:Prions / Q000187:drug effects*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000187:drug effects* / Q000502:physiology
D010455:Peptides; D011328:Prions; D000072235:Mating Factor; D019791:Guanidine