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Query: UNIPROT:P06889 (Mol)
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The UV induced mutation frequency of a given base pair located at different sites within the CYC1 gene of Saccharomyces cerevisiae was found to vary by more than fifty fold, indicating the existence of hotspots and coldspots typical of those found in other organisms. We were unable, however, to find any feature of the nucleotide sequence at or near the sites of mutation that explains this variability. These and other data suggest that hotspots are not located within regions particularly susceptible to the formation of premutational lesions. More probably the variation in mutability depends on differences in the activity of enzymes responsible for producing mutations, though the reasons for these differences are not understood and may depend on factors not directly related to nucleotide sequence.
Mol Gen Genet 1979
PMID:Absence of relationship between UV-induced reversion frequency and nucleotide sequence at the CYC1 locus of yeast. 23 28

The LPD1 gene of Saccharomyces cerevisiae, encoding lipoamide dehydrogenase (LPDH), is subject to catabolite repression. The promoter of this gene contains a number of motifs for DNA-binding transcriptional activators, including three which show strong sequence homology to the core HAP2/HAP3/HAP4 binding motif. Here we report that transcription of LPD1 requires HAP2, HAP3 and HAP4 for release from glucose repression. In the wild-type strain, specific activity of LPDH was increased 12-fold by growth on lactate, 10-fold on glycerol and four- to five-fold on galactose or raffinose, compared to growth on glucose. In hap2, hap3 and hap4 null mutants, the specific activities of LPDH in cultures grown on galactose and raffinose showed only slight induction above the basal level on glucose medium. Similar results were obtained upon assaying for beta-galactosidase production in wild-type, or hap2, hap3 or hap4 mutant strains carrying a single copy of the LPD1 promoter fused in frame to the lacZ gene of Escherichia coli and integrated at the URA3 locus. Transcript analysis in wild-type and hap2 mutants confirmed that the HAP2 protein regulates LPD1 expression at the level of transcription in the same way as it does for the CYC1 gene. Site-directed mutagenesis of the putative HAP2/HAP3/HAP4 binding site at -204 relative to the ATG start codon showed that this element was required for full derepression of the LPD1 gene on non-fermentable substrates.
Mol Gen Genet 1992 Jan
PMID:Positive regulation of the LPD1 gene of Saccharomyces cerevisiae by the HAP2/HAP3/HAP4 activation system. 131 May 23

Understanding the mechanism of glucose repression in yeast has proved to be a difficult and challenging problem. A multitude of genes in different pathways are repressed by glucose at the level of transcription. The SUC2 gene, which encodes invertase, is an excellent reporter gene for glucose repression, since its expression is controlled exclusively by this pathway. Genetic analysis has identified numerous regulatory mutations which can either prevent derepression of SUC2 or render its expression insensitive to glucose repression. These mutations allow us to sketch the outlines of a pathway for general glucose repression, which has several key elements: hexokinase PII, encoded by HXK2, which seems to play a role in the sensing of glucose levels; the protein kinase encoded by SNF1, whose activity is required for derepression of many glucose-repressible genes; and the MIG1 repressor protein, which binds to the upstream regions of SUC2 and other glucose-repressible genes. Repression by MIG1 requires the activity of the CYC8 and TUP1 proteins. Glucose repression of other sets of genes seems to be controlled by the general glucose repression pathway acting in concert with other mechanisms. In the cases of the GAL genes and possibly CYC1, regulation is mediated by a cascade in which the general pathway represses expression of a positive transcriptional activator.
Mol Microbiol 1992 Jan
PMID:Glucose repression in the yeast Saccharomyces cerevisiae. 131 Jul 93

Cleavage and polyadenylation of yeast precursor RNA require at least four functionally distinct factors (cleavage factor I [CF I], CF II, polyadenylation factor I [PF I], and poly(A) polymerase [PAP]) obtained from yeast whole cell extract. Cleavage of precursor occurs upon combination of the CF I and CF II fractions. The cleavage reaction proceeds in the absence of PAP or PF I. The cleavage factors exhibit low but detectable activity without exogenous ATP but are stimulated when this cofactor is included in the reaction. Cleavage by CF I and CF II is dependent on the presence of a (UA)6 sequence upstream of the GAL7 poly(A) site. The factors will also efficiently cleave precursor with the CYC1 poly(A) site. This RNA does not contain a UA repeat, and processing at this site is thought to be directed by a UAG...UAUGUA-type motif. Specific polyadenylation of a precleaved GAL7 RNA requires CF I, PF I, and a crude fraction containing PAP activity. The PAP fraction can be replaced by recombinant PAP, indicating that this enzyme is the only factor in this fraction needed for the reconstituted reaction. The poly(A) addition step is also dependent on the UA repeat. Since CF I is the only factor necessary for both cleavage and poly(A) addition, it is likely that this fraction contains a component which recognizes processing signals located upstream of the poly(A) site. The initial separation of processing factors in yeast cells suggests both interesting differences from and similarities to the mammalian system.
Mol Cell Biol 1992 Aug
PMID:Separation of factors required for cleavage and polyadenylation of yeast pre-mRNA. 135 51

A striking feature of the 3'-end regions in polymerase II transcripts of Saccharomyces cerevisiae adjacent to their processing and polyadenylation sites is the lack of well-defined signal elements. Nonetheless, essential signals have seemed to be confined to compact regions in vivo, and we find that a short RNA with only 70 bases of GAL7 sequence upstream and 8 to 10 bases downstream of the poly(A) addition site is processed in vitro, as is an analogous CYC1 pre-RNA. Specific polyadenylation of a precleaved species further delimits the poly(A) signal and rules out obligatory coupling between cleavage and poly(A) addition. Although little proximal and even less distal sequence is required for accurate cleavage with CYC1 and GAL7, we have been unable to identify common features to which processing could be ascribed. We therefore turned to the coregulated set of genes in the galactose cluster (GAL1, GAL7, and GAL10) to assay their corresponding pre-mRNAs in vitro, in hopes of finding a common theme. By contrast to GAL7, short pre-mRNAs corresponding to GAL1 and GAL10 fail to be cleaved detectably, and only much longer transcripts are susceptible to processing. This indicates that signals, even if preserved, are more widely dispersed than the poly(A) addition site, and these results are unchanged whether extracts are from cells grown on glucose or galactose. As a further surprise, RNAs corresponding to the antisense orientation of the 3'-end regions of all three GAL genes are also effective substrates for the processing machinery in vitro. Computer analysis reveals the presence of polydisperse dyad symmetries that might account for these observations.
Mol Cell Biol 1992 Oct
PMID:Unusual aspects of in vitro RNA processing in the 3' regions of the GAL1, GAL7, and GAL10 genes in Saccharomyces cerevisiae. 140 19

The ILV1 gene of Saccharomyces cerevisiae encodes the first committed step in isoleucine biosynthesis and is regulated by general control of amino acid biosynthesis. Deletion analysis of the ILV1 promoter revealed a GC-rich element important for the basal level expression. This cis-acting element, called ILV1BAS, is functional independently of whether GCN4 protein is present. Furthermore, unlike the situation at HIS4, the magnitude of GCN4-mediated derepression is independent of ILV1BAS. The element has homology to the consensus REB1-binding sequence CGGGTARNNR. Gel retardation assays showed that REB1 binds specifically to this element. We show that REB1-binding sites normally situated in the SIN3 promoter and in the 35S rRNA promoter can substitute for the ILV1 REB1 site. Furthermore, a SIN3 REB1 site containing a point mutation that abolishes REB1 binding does not support ILV1 basal level expression, suggesting that binding of REB1 is important for the control of ILV1 basal level expression. Interestingly, an ABF1-binding site can also functionally replace the ILV1 REB1-binding site. A mutated ABF1 site that displays a very low affinity for ABF1 does not functionally replace the ILV1 REB1 site. This suggests that ABF1 and REB1 may have related functions within the cell. Although the REB1-binding site is required for the ILV1 basal level expression, the site on its own stimulates transcription only slightly when combined with the CYC1 downstream promoter elements, indicating that another ILV1 promoter element functions in combination with the REB1 site to control high basal level expression.
Mol Cell Biol 1992 Dec
PMID:A REB1-binding site is required for GCN4-independent ILV1 basal level transcription and can be functionally replaced by an ABF1-binding site. 144 83

Using a gel retardation assay, a protein factor that specifically interacts with a 33 bp intragenic sequence of the highly expressed and glucose-inducible SRP1 gene of Saccharomyces cerevisiae has been detected. This binding site is located in a transcribed region and within the open reading frame (positions +710 to +743 relative to the first base of the initiation codon). A mutant strain carrying a deletion of this binding site showed a dramatic decrease in steady-state levels of SRP1 transcripts. This decline is not the result of a decrease in mRNA stability, since expression of hybrid genes in which the SRP1 promoter was replaced by the heterologous CYC1 promoter was not affected by the binding site deletion. These findings suggest that the 33 bp sequence contains a cis-acting downstream activating element which is involved in the transcriptional activation of the SRP1 promoter. Sequence comparisons showed similarities between a site located within the 33 bp sequence and the high-affinity consensus binding site of the RAP1/GRF1 (also named TUF) factor and methylation interference experiments confirmed that this site was involved in the protein-DNA interaction. Both the results of competition experiments with upstream activating sequences of ribosomal protein genes (UASrpg), which are targets for RAP1 binding, and determination of the apparent molecular weight of the affinity-purified DNA-binding protein indicated that RAP1 factor recognized the SRP1 33 bp element. The 33 bp sequence was found to be unable to provide UAS activity when placed upstream of the TATA box and transcription start site.
Mol Gen Genet 1992 Dec
PMID:Downstream activating sequence within the coding region of a yeast gene: specific binding in vitro of RAP1 protein. 149 52

In contrast to higher eukaryotes, little is known about the nature of the sequences which direct 3'-end formation of pre-mRNAs in the yeast Saccharomyces cerevisiae. The hexanucleotide AAUAAA, which is highly conserved and crucial in mammals, does not seem to have any functional importance for 3'-end formation in yeast cells. Instead, other elements have been proposed to serve as signal sequences. We performed a detailed investigation of the yeast ACT1, ADH1, CYC1, and YPT1 cDNAs, which showed that the polyadenylation sites used in vivo can be scattered over a region spanning up to 200 nucleotides. It therefore seems very unlikely that a single signal sequence is responsible for the selection of all these polyadenylation sites. Our study also showed that in the large majority of mRNAs, polyadenylation starts directly before or after an adenosine residue and that 3'-end formation of ADH1 transcripts occurs preferentially at the sequence PyAAA. Site-directed mutagenesis of these sites in the ADH1 gene suggested that this PyAAA sequence is essential for polyadenylation site selection both in vitro and in vivo. Furthermore, the 3'-terminal regions of the yeast genes investigated here are characterized by their capacity to act as signals for 3'-end formation in vivo in either orientation.
Mol Cell Biol 1992 Sep
PMID:Identification of pre-mRNA polyadenylation sites in Saccharomyces cerevisiae. 150 15

We have previously shown that nucleosome loss, obtained by repressing histone H4 mRNA synthesis, activates otherwise inactive PHO5, GAL1, and CYC1 gene promoters (fused to the bacterial beta-galactosidase [lacZ] reporter gene) to moderate levels of activity (approximately 2 to 15% of fully induced levels). We now report that nucleosome loss activates the expression of two additional promoters that are normally induced by independent mechanisms: CUP1 (induced by heavy-metal toxicity) and HIS3 (induced by amino acid starvation). Surprisingly, the level of CUP1-lacZ and HIS3-lacZ activation by nucleosome loss approximates fully induced levels of transcription. These CUP1 and HIS3 promoter activities are increased similarly from either episomal or genomic constructs. Our results emphasize the universality of the mechanism by which nucleosome loss activates yeast promoters. Moreover, a comparison of absolute levels of activation for different promoters suggests that activation by nucleosome loss results in a relatively constant level of activation, while levels obtained by normal induction vary considerably. These data argue that nucleosome loss may play a uniquely dominant role in the regulation of certain promoters.
Mol Cell Biol 1992 Apr
PMID:Nucleosome loss activates CUP1 and HIS3 promoters to fully induced levels in the yeast Saccharomyces cerevisiae. 154 16

Translation initiation factor eIF-5A is an abundant protein in which a lysine residue is modified by spermidine to form the amino acid derivative, hypusine. The factor is encoded by two genes in Saccharomyces cerevisiae, called TIF51A and TIF51B, which are regulated reciprocally by oxygen and by heme. TIF51B, also called ANB1, is located on chromosome X in a region called COR. We physically mapped TIF51A and its associated serine tRNA2 gene by the method of chromosome fragmentation and pulsed-field gel electrophoresis. TIF51A maps 90 kb from the left end of chromosome V in a region called ARC. The COR and ARC regions contain CYC1 and CYC7, respectively, and appear to be duplications carrying numerous related genes. The arrangements of related genes in the two regions are incompatible with a duplication mechanism involving a circular intermediate.
Mol Gen Genet 1992 Jun
PMID:The two genes encoding protein synthesis initiation factor eIF-5A in Saccharomyces cerevisiae are members of a duplicated gene cluster. 162 Jan 3


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