MAINTENANCE AND INHERITANCE OF YEAST PRIONS

The unusual genetic behaviour of two yeast extrachromosomal elements [ PSI] and [URE3] is entirely consistent with a prion-like mechanism of inheritance involving an autocatalytic alteration in the conformation of a normal cellular protein. In the case of both yeast determinants t he identity of the underlying cellular prion protein is known. The dis covery that the molecular chaperone Hsp104 is essential for the establ ishment and maintenance of the [PSI] determinant provides an explanati on for several aspects of the puzzling genetic behaviour of these dete rminants. What remains to be explained is whether these determinants r epresent 'disease states' of yeast or represent the first examples of a unique mechanism for producing a heritable change in phenotype witho ut an underlying change in genotype.