Overexpression of Hsp104 by Causing Dissolution of the Prion Seeds Cures the Yeast [PSI+] Prion

The yeast Sup35 protein misfolds into the infectious [PSI+] prion, which is then propagated by the severing activity of the molecular chaperone, Hsp104. Unlike other yeast prions, this prion is unique in that it is efficiently cured by the overexpression as well as the inactivation of Hsp104. However, it is controversial whether curing by overexpression is due to the dissolution of the prion seeds by the trimming activity of Hsp104 or the asymmetric segregation of the prion seeds between mother and daughter cells which requires cell division. To answer this question, we conducted experiments and found no difference in the extent of curing between mother and daughter cells when half of the cells were cured by Hsp104 overexpression in one generation. Furthermore, curing was not affected by the lack of Sir2 expression, which was reported to be required for asymmetric segregation of the [PSI+] seeds. More importantly, when either hydroxyurea or ethanol were used to inhibit cell division, the extent of curing by Hsp104 overexpression was not significantly reduced. Therefore, the curing of [PSI+] by Hsp104 overexpression is not due to asymmetric segregation of the prion seeds, but rather their dissolution by Hsp104.

Automated summary

The yeast Sup35 protein misfolds into the infectious [PSI+] prion, which is propagated by Hsp104. Unlike other yeast prions, this prion is efficiently cured by overexpression or inactivation of Hsp104. The extent of curing is not affected by asymmetric segregation or inhibition of cell division, indicating that Hsp104 overexpression leads to prion dissolution.