Yeast self-perpetuating protein aggregates (prions) provide a convenient model for studying various components of the cellular protein quality control system. Molecular chaperones and chaperone-sorting factors, such as yeast Cur1 protein, play key role in proteostasis via tight control of partitioning and recycling of misfolded proteins. In this study, we show that, despite the previously described ability of Cur1 to antagonize the yeast prion [URE3], it enhances propagation and phenotypic manifestation of another prion, [PSI ]. We demonstrate that both curing of [URE3] and enhancement of [PSI ] in the presence of excess Cur1 are counteracted by the cochaperone Hsp40-Sis1 in a dosage-dependent manner, and show that the effect of Cur1 on prions parallels effects of the attachment of nuclear localization signal to Sis1, indicating that Cur1 acts on prions via its previously reported ability to relocalize Sis1 from the cytoplasm to nucleus. This shows that the direction in which Cur1 influences a prion depends on how this specific prion responds to relocalization of Sis1.

Background : The termination of protein synthesis in eukaryotes involves at least two polypeptide release factors (eRFs), eRF1 and eRF3. In mammals two genes encoding eRF3 structural homologues were identified and named GSPT1 and GSPT2.

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The study of the SUP45 and SUP35 genes of yeast Saccharomyces cerevisiae in the laboratory of Physiological Genetics of St. Petersburg State University began in 1964 when the first omnipotent nonsense suppressor mutations were obtained. During the following 55 years, a lot of information about these genes has been gained through the research efforts of various laboratories. Now we know that SUP45 and SUP35 encode translation termination factors eRF1 and eRF3, respectively. Both genes are essential, and sup45 and sup35 mutations lead not only to impaired translation but also to multiple pleiotropic effects. The aim of this review is to summarize known data about suppressor mutations in SUP45 or SUP35 genes.

Mutations in the essential genes SUP45 and SUP35, encoding yeast translation termination factors eRF1 and eRF3, respectively, lead to a wide range of phenotypes and affect various cell processes. In this work, we show that nonsense and missense mutations in the SUP45, but not the SUP35, gene abolish diploid pseudohyphal and haploid invasive growth. Missense mutations that change phosphorylation sites of Sup45 protein do not affect the ability of yeast strains to form pseudohyphae. Deletion of the C-terminal part of eRF1 did not lead to impairment of filamentation. We show a correlation between the filamentation defect and the budding pattern in sup45 strains. Inhibition of translation with specific antibiotics causes a significant reduction in pseudohyphal growth in the wild-type strain, suggesting a strong correlation between translation and the ability for filamentous growth. Partial restoration of pseudohyphal growth by addition of exogenous cAMP assumes that sup45 mutants are defective in the cAMP-dependent pathway that control filament formation.

Multiple drug resistance (MDR) to widening range of antibiotics emerging in increasing variety of pathogenic bacteria is a serious threat to the health of mankind nowadays. This is partially due to an uncontrolled usage of antibiotics not only in clinical practice, but also in various branches of agriculture. MDR is affected by two mechanisms: (1) accumulation of resistance genes as a result of intensive selection caused by antibiotics, and (2) active horizontal transfer of resistance genes. To unveil the reasons of bacterial multiresistance to antibiotics, it is necessary to understand the mechanisms of antibiotics action as well as the ways how either resistance to certain antibiotics emerge or resistance genes accumulate and transfer among bacterial strains. Current review is devoted to all these problems.

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