Suppressors in Yeast

Hawthorne, Donald C.; Leupold, Urs

doi:10.1007/978-3-642-65848-8_1

Cited by 234 publications

(71 citation statements)

References 80 publications

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“…Since, suppression became the main genetic approach to investigate translation mechanisms and has been widely used in different organisms. Hawthorne and Mortimer (1963) described two unlinked dominant suppressors, that can suppress about 1/3 of all mutations (14 of 40) studied in 11 genes of S. cerevisiae. A study of supersuppressible alleles in TRP5 (tryptophansynthetase) gene by Manney (1964) showed their restricted ability to interallelic complementation (an ability to restore pseudo-wild phenotype in pairwise combinations; this character is specific to genes encoding proteins composed of identical subunits).…”

Section: Concepts and Facts Came First From Prokaryotesmentioning

confidence: 99%

“…The genes with comparable characteristics when mutated had been described repeatedly and given different names by several groups-SUP1: SUP45 (Hawthorne and Leupold, 1974), SUPQ (Gerlach, 1975), SUP47 (Ono et al, 1984), SAL4 (Crouzet et al, 1988); SUP2: SUP35 (Hawthorne and Leupold, 1974), SUP36 (Ono et al, 1984), SUPP (Gerlach, 1975), SAL3 (Crouzet and Tuite, 1987); GST1 (Kikuchi et al, 1988). Finally in accordance with the internationally accepted nomenclature these two genes were named SUP45 and SUP35.…”

Section: Identification Of Sup45 and Sup35 Genes In Saccharomyces Cermentioning

confidence: 99%

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Eukaryotic release factors (eRFs) history

Инге-Вечтомов

Zhouravleva

Maury

2003

Biology of the Cell

112

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In the present review, we describe the history of the identification of the eukaryotic translation termination factors eRF1 and eRF3. As in the case of several proteins involved in general and essential processes in all cells (e.g., DNA replication, gene expression regulation...) the strategies and methodologies used to identify these release factors were first established in prokaryotes. The genetic investigations in Saccharomyces cerevisiae have made a major contribution in the field. A large amount of data have been produced, from which it was concluded that the SUP45 and SUP35 genes were controlling translation termination but were also involved in other functions important for the cell organization and the cell cycle accomplishment. This does not seem to be restricted to yeast but is also probably the case in eukaryotes in general. The biochemical studies of the proteins encoded by the higher eukaryote homologs of SUP45 and SUP35 were efficient and permitted the identification of eRF1 as being the key protein in the termination process, eRF3 having a stimulating role. Around 25 years were needed after the identification of sup45 and sup35 mutants for the characterization of their gene products as eRF1 and eRF3, respectively. It also has to be pointed out that if the results came first from bacteria, the identification of RF3 and eRF3 was made practically at the same time. Moreover, eRF1 was the first crystal structure obtained for a class-1 release factor, the bacterial RF2 structure came later. The goal is now to understand at the molecular level the roles of both eRF1 and eRF3 in addition to their translation termination functions.

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Section: Concepts and Facts Came First From Prokaryotesmentioning

confidence: 99%

Section: Identification Of Sup45 and Sup35 Genes In Saccharomyces Cermentioning

confidence: 99%

Eukaryotic release factors (eRFs) history

Инге-Вечтомов

Zhouravleva

Maury

2003

Biology of the Cell

112

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“…These mutations require increasing levels of SUP4 tRNA Tyr in order to be suppressed, that is, met4-1 o is sup- pressed by low levels, lys2-1 o is suppressed by intermediate levels, and the ade2-1 o mutation requires high levels of expression of the SUP4 gene (Hawthorne and Leupold 1974). This difference is due to the functionality of the mutated protein in which the tyrosine amino acid is inserted as a replacement for the wild-type amino acid.…”

Section: Sup4 Pre-trna Archeuka Tyr Is Functional In Vivomentioning

confidence: 99%

A pre-tRNA carrying intron features typical of Archaea is spliced in yeast

Segni¹,

Borghese²,

Sebastiani³

et al. 2004

RNA

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Archaeal pre-tRNAs are characterized by the presence of the bulge-helix-bulge (BHB) structure in the intron stem-and-loop region. A chimeric pre-tRNA was constructed bearing an intron of the archaeal type and the mature domain of the Saccharomyces cerevisiae suppressor SUP4 tRNA Tyr . This pre-tRNA ArchEuka is correctly cleaved in several cell-free extracts and by purified splicing endonucleases. It is also cleaved and ligated in S. cerevisiae cells, providing efficient suppression of nonsense mutations in various genes.

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“…sup45 and a more recently isolated omnipotent suppressor, sup46 (31), map near lys2 on chromosome 2R but are presumably distinct (31), and sup35 is on chromosome 4R (15). Unlike tRNA suppressors, omnipotent suppressors are usually recessive; they display a variety of allele-specific pleiotropic effects in vivo, including osmotic sensitivity, high or low temperature sensitivity, respiratory deficiency, and sensitivity to aminoglycoside antibiotics such as paromomycin (15,19,46,47). Ribosomes isolated from omnipotent suppressor strains have been reported to show increased misreading in vitro (43,44) and, at least for sup46 (26), this misreading is enhanced by paromomycin.…”

mentioning

confidence: 99%

Isolation of the SUP45 omnipotent suppressor gene of Saccharomyces cerevisiae and characterization of its gene product.

Himmelfarb¹,

Maicas²,

Friesen³

1985

Mol. Cell. Biol.

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The Saccharomyces cerevisiae SUP45+ gene has been isolated from a genomic clone library by genetic complementation of paromomycin sensitivity, which is a property of a mutant strain carrying the sup45-2 allele. This plasmid complements all phenotypes associated with the sup45-2 mutation, including nonsense suppression, temperature sensitivity, osmotic sensitivity, and paromomycin sensitivity. Genetic mapping with a URA3+-marked derivative of the complementing plasmid that was integrated into the chromosome by homologous recombination demonstrated that the complementing fragment contained the SUP45+ gene and not an unlinked suppressor. The SUP45+ gene is present as a single copy in the haploid genome and is essential for viability. In vitro translation of the hybrid-selected SUP45+ transcript yielded a protein of Mr = 54,000, which is larger than any known ribosomal protein. RNA blot hybridization analysis showed that the steady-state level of the SUP45' transcript is less than 10% of that for ribosomal protein L3 or rp59 transcripts. When yeast cells are subjected to a mild heat shock, the synthesis rate of the SUP45+ transcript was transiently reduced, approximately in parallel with ribosomal protein transcripts. Our data suggest that the SUP45+ gene does not encode a ribosomal protein. We speculate that it codes for a translation-related function whose precise nature is not yet known.Omnipotent suppressor mutants of the yeast Saccharomyces cerevisiae are named for their ability to suppress simultaneously UAG, UGA, and UAA nonsense mutations. These suppressors were first identified by IngeVechtomov and Andrianova (19) and were mapped to two loci that have been designated sup35 and sup45 (15), sup2 and supi (19), or supP and supQ (10). sup45 and a more recently isolated omnipotent suppressor, sup46 (31), map near lys2 on chromosome 2R but are presumably distinct (31), and sup35 is on chromosome 4R (15). Unlike tRNA suppressors, omnipotent suppressors are usually recessive; they display a variety of allele-specific pleiotropic effects in vivo, including osmotic sensitivity, high or low temperature sensitivity, respiratory deficiency, and sensitivity to aminoglycoside antibiotics such as paromomycin (15,19,46,47). Ribosomes isolated from omnipotent suppressor strains have been reported to show increased misreading in vitro (43,44) and, at least for sup46 (26), this misreading is enhanced by paromomycin. Paromomycin induces phenotypic suppression of nonsense and presumed missense mutations (4, 42) and has been shown to decrease the fidelity of translation in vitro, both in S. cerevisiae (33, 42) and in Escherichia coli (5) by binding to ribosomes (33). In vivo, sup45 and paromomycin have been shown to act synergistically in their suppression of nonsense mutations of nutritional markers (46). Ribosomes purified from sup] (sup45) mutant strains show an increased dissociability into subunits in vivo (44).One low-temperature-sensitive allele of supi (reference 45) is defective in 60S subunit assembly. All in all, th...

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Suppressors in Yeast

Cited by 234 publications

References 80 publications

Eukaryotic release factors (eRFs) history

Eukaryotic release factors (eRFs) history

A pre-tRNA carrying intron features typical of Archaea is spliced in yeast

Isolation of the SUP45 omnipotent suppressor gene of Saccharomyces cerevisiae and characterization of its gene product.

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