Investigating protein conformation-based inheritance and disease in yeast

S. Lindquist*, S. Krobitsch, L. Li, N. Sondheimer, H. Peto, C. M. Dobson, M. F. Perutz, M. Pepys, M. E. Goldberg

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Our work supports the hypothesis that a protein can serve as an element of genetic inheritance. This protein-only mechanism of inheritance is propagated in much the same way as hypothesized for the transmission of the protein-only infectious agent in the spongiform encephalopathies; hence these protein factors have been called yeast prions. Our work has focused on [PSI+], a dominant cytoplasmically inherited factor that alters translational fidelity. This change in translation is produced by a self-perpetuating change in the conformation of the translation-termination factor, Sup35. Most recently, we have determined that new elements of genetic inheritance can be created by deliberate genetic engineering, opening prospects for new methods of manipulating heredity. We have also uncovered evidence that other previously unknown elements of protein-based inheritance are encoded in the yeast genome. Finally, we have begun to use yeast as a model system for studying human protein folding diseases, such as Huntington's disease. Proteins responsible for some of these diseases have properties uncannily similar to those that produce protein-based mechanisms of inheritance.

Original languageEnglish (US)
Pages (from-to)169-176
Number of pages8
JournalPhilosophical Transactions of the Royal Society B: Biological Sciences
Issue number1406
StatePublished - Feb 28 2001


  • Amyloid
  • Epigenetic
  • Huntington's disease
  • PSI
  • Prion
  • Sup35

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)


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