Genetics, Vol 144, 1375-1386, Copyright © 1996


INVESTIGATIONS

Genesis and Variability of [PS1] Prion Factors in Saccharomyces cerevisiae

I. L. Derkatch, Y. O. Chernoff, V. V. Kushnirov, S. G. Inge-Vechtomov and S. W. Liebman
Laboratory for Molecular Biology, Department of Biological Sciences, University of Illinois at Chicago, Chicago, Illinois 60607, Laboratory of Physiological Genetics, Department of Genetics, St. Petersburg State University, 199034 St. Petersburg, Russia

We have previously shown that multicopy plasmids containing the complete SUP35 gene are able to induce the appearance of the non-Mendelian factor [PS1]. This result was later interpreted by others as a crucial piece of evidence for a model postulating that [PS1] is a self-modified, prion-like conformational derivative of the Sup35 protein. Here we support this interpretation by proving that it is the overproduction of Sup35 protein, and not the excess of SUP35 DNA or mRNA that causes the appearance of [PS1]. We also show that the ``prion-inducing domain'' of Sup35p is in the N-terminal region, which, like the ``prion-inducing domain'' of another yeast prion, Ure2p, was previously shown to be distinct from the functional domain of the protein. This suggests that such a chimeric organization may be a common pattern of some prion elements. Finally, we find that [PS1] factors of different efficiencies and different mitotic stabilities are induced in the same yeast strain by overproduction of the identical Sup35 protein. We suggest that the different [PS1]-containing derivatives are analogous to the mysterious mammalian prion strains and result from different conformational variants of Sup35p.


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