Respiratory deficiency of sup45 mutants may be compensated epigenetically.
Kirill Osipov, Kirill Volkov, Ludmila Mironova
Dep. of Genetics and Breeding, St.Petersburg State University, Universitetskaya emb, St. Petersburg, 199034, Russian Federation
The SUP45 gene of Saccharomyces cerevisiae encodes eRF1 release factor. sup45 mutations cause nonsense suppression due to decrease of translation termination efficiency. In addition, many of them cause respiratory deficiency manifesting as inability to use nonfermentable substrates. Usually, this phenotype is unstable and reversions to respiratory competence arise with a high frequency. These reversions may be caused by dominant and recessive nuclear mutations as well as by determinants demonstrating a nonchromosomal inheritance. The latter group of reversions displays some attributes of mitochondrial inheritance, since elimination of mtDNA causes the loss of compensating determinant, revealed by subsequent genetic analysis. From the other hand, these reversions are mitotically unstable, but their loss during mitosis is not related to any damage or elimination of mitochondrial genome. Importantly, the frequency of their loss in mitosis may be essentially increased both by the GuHCl treatment (universal antiprion agent) and by overproduction of the chaperone Hsp104 playing a key role in propagation of yeast prions. Thus, compensation of respiratory deficiency caused by sup45 mutations is probably related to an unknown epigenetic (prion) determinant dependent in some way on mtDNA. The nature of this determinant as well as its intracellular localization remains to be established. The work was supported by RFBR 02-04-49699 and CRDF ST-012 grants.