TY - JOUR
T1 - Genetic and environmental factors affecting the de novo appearance of the [PSI+] prion in Saccharomyces cerevisiae
AU - Derkatch, Irina L.
AU - Bradley, Michael E.
AU - Zhou, Ping
AU - Chernoff, Yury O.
AU - Liebman, Susan W.
PY - 1997/10/1
Y1 - 1997/10/1
N2 - It has previously been shown that yeast prion [PSI+] is cured by GuHCl, although reports on reversibility of curing were contradictory. Here we show that GuHCl treatment of both [PSI+] and [psi-] yeast strains results in two classes of [psi-] derivatives: Pin+, in which [PSI+] can be reinduced by Sup35p overproduction, and Pin-, in which overexpression of the complete SUP35 gene does not lead to the [PSI+] appearance. However, in both Pin+ and Pin- derivatives [PSI+] is reinduced by overproduction of a short Sup35p N-terminal fragment, thus, in principle, [PSI+] curing remains reversible in both cases. Neither suppression nor growth inhibition caused by SUP35 overexpression in Pin+ [psi-] derivatives are observed in Pin- [psi-] derivatives. Genetic analyses show that the Pin+ phenotype is determined by a non-Mendelian factor, which, unlike the [PSI+] prion, is independent of the Sup35p N-terminal domain. A Pin- [psi-] derivative was also generated by transient inactivation of the heat shock protein, Hsp104, while [PSI+] curing by Hsp104 overproduction resulted exclusively in Pin+ [psi-] derivatives. We hypothesize that in addition to the [PSI+] prion- determining domain in the Sup35p N-terminus, there is another self- propagating conformational determinant in the C-proximal part of Sup35p and that this second prion is responsible for the Pin+ phenotype.
AB - It has previously been shown that yeast prion [PSI+] is cured by GuHCl, although reports on reversibility of curing were contradictory. Here we show that GuHCl treatment of both [PSI+] and [psi-] yeast strains results in two classes of [psi-] derivatives: Pin+, in which [PSI+] can be reinduced by Sup35p overproduction, and Pin-, in which overexpression of the complete SUP35 gene does not lead to the [PSI+] appearance. However, in both Pin+ and Pin- derivatives [PSI+] is reinduced by overproduction of a short Sup35p N-terminal fragment, thus, in principle, [PSI+] curing remains reversible in both cases. Neither suppression nor growth inhibition caused by SUP35 overexpression in Pin+ [psi-] derivatives are observed in Pin- [psi-] derivatives. Genetic analyses show that the Pin+ phenotype is determined by a non-Mendelian factor, which, unlike the [PSI+] prion, is independent of the Sup35p N-terminal domain. A Pin- [psi-] derivative was also generated by transient inactivation of the heat shock protein, Hsp104, while [PSI+] curing by Hsp104 overproduction resulted exclusively in Pin+ [psi-] derivatives. We hypothesize that in addition to the [PSI+] prion- determining domain in the Sup35p N-terminus, there is another self- propagating conformational determinant in the C-proximal part of Sup35p and that this second prion is responsible for the Pin+ phenotype.
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M3 - Article
C2 - 9335589
AN - SCOPUS:0030833388
VL - 147
SP - 507
EP - 519
JO - Genetics
JF - Genetics
SN - 0016-6731
IS - 2
ER -