Neurodegeneration is linked to protein aggregation in several human disorders. In Huntington's disease, the length of a polyglutamine stretch in Huntingtin is correlated to neuronal death. Here we utilize a model based on glutamine stretches of 0, 30 or 56 residues in Saccharomyces cerevisiae to understand how such toxic proteins interfere with cellular physiology. A toxicity-mimicking cytostatic effect is evident from compromised colony formation upon expression of polyglutamines. Interestingly, diploid cells are insensitive to polyglutamines and haploid cells can escape cytostasis by hyperploidization. Using a genome-wide screen for genes required to obtain the cytostatic effect, we identify a network related to the budding process and cellular division. We observe a striking mislocalization of the septins Cdc10 and Shs1 in cells arrested by polyglutamines, suggesting that the septin ring may be a pivotal structure connecting polyglutamine toxicity and ploidy.
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Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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Site | Modification | Modifier | Source | Reference |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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Evidence ID | Analyze ID | File | Description |
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