Abstract
Previously, we proposed a test system that allows one to search for genes that influence the properties of Sup35 and Sup45 proteins. This test is based on the phenomenon of the lethality of diploids that combine mutations in the SUP45 gene with [PSI +] prion. The lethality of this combination depends on both the type of sup45 mutation and the properties of the prion. The [PSI +] variant, which is a strong suppressor ([PSI +]S), causes synthetic lethality with all the nonsense mutations and some missense sup45 mutations in the heterozygote state. The presence of extra copies of the tested gene, which affects the phenotypic manifestation of the prion [PSI +] or properties of the termination factors of translation leads to a increase or decrease in diploid lethality. The screening of the gene library using this test system allowed us to establish the effect of ten fragments of genomic DNA of yeast on synthetic lethality. The deletion analysis of these regions has led to the identification of the HLJ1 and TEF2 genes, which affects the prionization of the Sup35 protein and/or the efficiency of translation termination.
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Zhouravleva G., Frolova L., Le Goff X., Le Guellec R., Inge-Vechtomov S., Kisselev L., Philippe M. 1995. Termination of translation in eukaryotes is governed by two interacting polypeptide chain release factors, eRF1 and eRF3. EMBO J. 14, 4065–4072.
Stansfield I., Jones K.M., Kushnirov V.V., Dagkesamanskaya A.R., Poznyakovski A.I., Paushkin S.V., Nierras C.B., Cox B.S., Ter-Avanesyan M.D., Tuite M.F. 1995. The products of the SUP45 (eRF1) and SUP35 genes interact to mediate translation termination in Saccharomyces cerevisiae. EMBO J. 14, 4365–4373.
Patino M.M., Liu J.J., Glover J.R., Lindquist S. 1996. Support for the prion hypothesis for inheritance of a phenotypic trait in yeast. Science. 273, 622–626.
Paushkin S.V., Kushnirov V.V., Smirnov V.N., Ter-Avanesyan M.D. 1996. Propagation of the yeast prionlike [psi +] determinant is mediated by oligomerization of the SUP35-encoded polypeptide chain release factor. EMBO J. 15, 3127–3134.
Cox B.S. 1965. PSI+, a cytoplasmic suppressor of supersuppressor in yeast. Heredity. 20, 505–521.
Liebman S.W., Sherman F. 1979. Extrachromosomal psi+ determinant suppresses nonsense mutations in yeast. J. Bacteriol. 139, 1068–1071.
Alberti S., Halfmann R., King O., Kapila A., Lindquist S. 2009. A systematic survey identifies prions and illuminates sequence features of prionogenic proteins. Cell. 137, 146–158.
Tuite M.F., Cox B.S. 2007. The genetic control of the formation and propagation of the [PSI+] prion of yeast. Prion. 1, 101–109.
Derkatch I.L., Chernoff Y.O., Kushnirov V.V., Inge-Vechtomov S.G., Liebman S.W. 1996. Genesis and variability of [PSI] prion factors in Saccharomyces cerevisiae. Genetics. 144, 1375–1386.
Tuite M.F., Mundy C.R., Cox B.S. 1981. Agents that cause a high frequency of genetic change from [psi +] to [psi −] in Saccharomyces cerevisiae. Genetics. 98, 691–711.
Cox B.S., Tuite M.F., McLaughlin C.S. 1988. The psi factor of yeast: A problem in inheritance. Yeast. 4, 59–178.
Kiktev D., Inge-Vechtomov S.G., Zhouravleva G. 2007. Prion-dependent lethality of sup45 mutants in Saccharomyces cerevisiae. Prion. 1, 136–143.
Chernoff Y.O., Lindquist S.L., Ono B., Inge-Vechtomov S.G., Liebman S.W. 1995. Role of the chaperone protein Hsp104 in propagation of the yeast prion-like factor [psi+]. Science. 268, 880–884.
Chernoff Y.O., Newnam G.P., Kumar J., Allen K., Zink A.D. 1999. Evidence for a protein mutator in yeast: role of the Hsp70-related chaperone ssb in formation, stability, and toxicity of the [PSI] prion. Mol. Cell. Biol. 19, 8103–8112.
Newnam G.P., Wegrzyn R.D., Lindquist S.L., Chernoff Y.O. 1999. Antagonistic interactions between yeast chaperones Hsp104 and Hsp70 in prion curing. Mol. Cell. Biol. 19, 1325–1333.
Kryndushkin D.S., Smirnov V.N., Ter-Avanesyan M.D., Kushnirov V.V. 2002. Increased expression of Hsp40 chaperones, transcriptional factors and ribosomal protein Rpp0 can cure yeast prions. J. Biol. Chem. 277, 23702–23708.
Liebman S.W., All-Robyn J.A. 1984. A non-mendelian factor, [eta +], causes lethality of yeast omnipotent-suppressor strains. Curr. Genet. 8, 567–573.
All-Robyn J.A., Kelley-Geraghty D., Griffin E., Brown N., Liebman S.W. 1990. Isolation of omnipotent suppressors in an [eta +] yeast strain. Genetics. 124, 505–514.
Tikhodeev O.N., Getmanova E.V., Tikhomirova V.L., Inge-Vechtomov S.G. 1990. Ambiguity of translation in yeast: Genetic control and modifications. In: Molekulyarnye mekhanizmy geneticheskikh protsessov (Molecular Mechanisms of Genetic Processes). Moscow: Nauka, pp. 218–228.
Kiktev D.A., Chernov Yu.O., Arkhipenko A.V., Zhuravleva G.A. 2011. Identification of genes influencing synthetic lethality of genetic and epigenetic changes in translation termination factors in yeasr. Doklady Akad. Nauk. 438, 416–418.
Sambrook J., Fritsch E.F., Maniatis T. 1989. Molecular Cloning: A Laboratory Manual. Cold Spring Harbor, NY: Cold Spring Harbor Lab. Press.
Moskalenko S.E., Chabelskaya S.V., Inge-Vechtomov S.G., Philippe M., Zhouravleva G.A. 2003. Viable nonsense mutants for the essential gene SUP45 of Saccharomyces cerevisiae. BMC Mol. Biol. 4, 2.
Moskalenko S.E., Zhuravleva G.A., Soom M.I., Shabel’skaya S.V., Volkov K.V., Zemlyanko O.M., Filipp M., Mironova L.N., Inge-Vechtomov S.G. 2004. Characterization of missense mutations in the SUP45 gene of Saccharomyces cerevisiae encoding translation termination factor eRF1. Russ. J. Genet. 40, 478–484.
Sikorski R.S., Hieter P. 1989. A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics. 122, 19–27.
Rubel’ A.A., Korzhova V.V., Saifitdinova A.F., Antonets K.S., Inge-Vechtomov S.G., Galkin A.P. 2012. The PrP protein and amyloid beta interact in yeast Saccharomyces cerevisiae. Ekol. Genet. 10, 74–80.
Valouev I.A., Fominov G.V., Sokolova E.E., Smirnov V.N., Ter-Avanesyan M.D. 2009. Elongation factor eEF1B modulates functions of the release factors eRF1 and eRF3 and the efficiency of translation termination in yeast. BMC Mol. Biol. 10, 60.
Guthrie C., Fink G.R. 1991. Guide to Yeast Genetics and Molecular Biology. San Diego: Academic Press.
Rose M.D., Winston F.M., Hieter P., Sherman F. 1990. Methods in Yeast Genetics: A Laboratory Course Manual. Cold Spring Harbor, NY: Cold Spring Harbor Lab. Press.
Kaiser C., Michaelis S., Mitchell A. 1994. Methods in Yeast Genetics. Cold Spring Harbor, NY: Cold Spring Harbor Lab. Press.
Gietz R.D., Schiestl R.H., Willems A.R., Woods R.A. 1995. Studies on the transformation of intact yeast cells by the LiAc/SS-DNA/PEG procedure. Yeast. 11, 355–360.
Elble R., Tye B.K. 1991. Both activation and repression of a-mating-type-specific genes in yeast require transcription factor Mcm1. Proc. Natl. Acad. Sci. U. S. A. 88, 10966–10970.
Bruhn L., Hwang-Shum J.J., Sprague G.F., Jr. 1992. The N-terminal 96 residues of MCM1, a regulator of cell type-specific genes in Saccharomyces cerevisiae, are sufficient for DNA binding, transcription activation, and interaction with alpha 1. Mol. Cell. Biol. 12, 3563–3572.
Michelitsch M.D., Weissman J.S. 2000. A census of glutamine/asparagine-rich regions: Implications for their conserved function and the prediction of novel prions. Proc. Natl. Acad. Sci. U. S. A. 97, 11910–11915.
Valente L., Kinzy T.G. 2003. Yeast as a sensor of factors affecting the accuracy of protein synthesis. Cell. Mol. Life Sci. 60, 2115–2130.
Szabo A., Langer T., Schroder H., Flanagan J., Bukau B., Hartl F.U. 1994. The ATP hydrolysis-dependent reaction cycle of the Escherichia coli Hsp70 system DnaK, DnaJ, and GrpE. Proc. Natl. Acad. Sci. U. S. A. 91, 10345–10349.
Cyr D.M., Lu X., Douglas M.G. 1992. Regulation of Hsp70 function by an eukaryotic DnaJ homolog. J. Biol. Chem. 267, 20927–20931.
Langer T., Lu C., Echols H., Flanagan J., Hayer M.K., Hartl F.U. 1992. Successive action of DnaK, DnaJ and GroEL along the pathway of chaperone-mediated protein folding. Nature. 356, 683–689.
Qiu X.B., Shao Y.M., Miao S., Wang L. 2006. The diversity of the DnaJ/Hsp40 family, the crucial partners for Hsp70 chaperones. Cell. Mol. Life Sci. 63, 2560–2570.
Huyer G., Piluek W.F., Fansler Z., Kreft S.G., Hochstrasser M., Brodsky J.L., Michaelis S. 2004. Distinct machinery is required in Saccharomyces cerevisiae for the endoplasmic reticulum-associated degradation of a multispanning membrane protein and a soluble luminal protein. J. Biol. Chem. 279, 38369–38378.
Mead J., Bruning A.R., Gill M.K., Steiner A.M., Acton T.B., Vershon A.K. 2002. Interactions of the Mcm1 MADS box protein with cofactors that regulate mating in yeast. Mol. Cell. Biol. 22, 4607–4621.
Christ C., Tye B.K. 1991. Functional domains of the yeast transcription/replication factor MCM1. Genes Dev. 5, 751–763.
Meriin A.B., Zhang X., He X., Newnam G.P., Chernoff Y.O., Sherman M.Y. 2002. Huntington toxicity in yeast model depends on polyglutamine aggregation mediated by a prion-like protein Rnq1. J. Cell Biol. 157, 997–1004.
Carr-Schmid A., Valente L., Loik V.I., Williams T., Starita L.M., Kinzy T.G. 1999. Mutations in elongation factor 1beta, a guanine nucleotide exchange factor, enhance translational fidelity. Mol. Cell. Biol. 19, 5257–5266.
Beier H., Grimm M. 2001. Misreading of termination codons in eukaryotes by natural nonsense suppressor tRNAs. Nucleic Acids Res. 29, 4767–4782.
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Original Russian Text © A.G. Matveenko, O.M. Zemlyanko, G.A. Zhouravleva, 2013, published in Molekulyarnaya Biologiya, 2013, Vol. 47, No. 4, pp. 609–617.
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Matveenko, A.G., Zemlyanko, O.M. & Zhouravleva, G.A. Identification of Saccharomyces cerevisiae genes leading to synthetic lethality of prion [PSI +] with SUP45 mutations. Mol Biol 47, 530–537 (2013). https://doi.org/10.1134/S0026893313040110
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DOI: https://doi.org/10.1134/S0026893313040110