Cell division is essential for elimination of the yeast [PSI+] prion by guanidine hydrochloride

Guanidine hydrochloride (Gdn center dot 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 center dot HCl-induced loss of the [PSI+] prion. Subsequently, Wu et al. [Wu Y, Greene LE, Masison DC, Eisenberg E (2005) Proc Nat] Acad Sci USA 102:1278912794] claimed to show that Gdn center dot HCl can eliminate the [PSI+] prion from alpha-factor-arrested cells leading them to propose that in Gdn center dot HCl center dot 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 center dot HCl requires ongoing cell division and that prions are not destroyed during or after the evident curing phase.