Giorgini F~Muchowski PJ, 2005

Pubmed ID 15806102
Title A genomic screen in yeast implicates kynurenine 3-monooxygenase as a therapeutic target for Huntington disease.
Authors Flaviano Giorgini, Paolo Guidetti, QuangVu Nguyen, Simone C Bennett, Paul J Muchowski
Abstract Huntington disease is a fatal neurodegenerative disorder caused by expansion of a polyglutamine tract in the protein huntingtin (Htt), which leads to its aggregation in nuclear and cytoplasmic inclusion bodies. We recently identified 52 loss-of-function mutations in yeast genes that enhance the toxicity of a mutant Htt fragment. Here we report the results from a genome-wide loss-of-function suppressor screen in which we identified 28 gene deletions that suppress toxicity of a mutant Htt fragment. The suppressors are known or predicted to have roles in vesicle transport, vacuolar degradation, transcription and prion-like aggregation. Among the most potent suppressors was Bna4 (kynurenine 3-monooxygenase), an enzyme in the kynurenine pathway of tryptophan degradation that has been linked directly to the pathophysiology of Huntington disease in humans by a mechanism that may involve reactive oxygen species. This finding is suggestive of a conserved mechanism of polyglutamine toxicity from yeast to humans and identifies new candidate therapeutic targets for the treatment of Huntington disease.
Citation Nat Genet 2005; 37:526-31
Data abstract Deletion collection was tested for toxicity from expression of huntingtin (Htt103Q)


Download the list of datasets
Paper Phenotype Condition Medium Collection Tested mutants Data Details
Giorgini F~Muchowski PJ, 2005 growth (pooled CFU) expression of mutant huntingtin fragment [GAL] SC - Ura, Gal [2%] hap a 4,838 Discrete

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Tested strains

Feb. 25, 2014 Request sent.
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