Synthetic Lethality Induced by Toxic Polyglutamine Tract II: A Survey in Drosophila

摘要: Mutant proteins containing an expanded polyglutamine tract induce cell death and cause neurodegenerative diseases. These toxic interfere with a variety of physiological pathways, but the key interactions between toxins cellular factors remain unclear. To model diseases in Drosophila, GMR-Gal4/UAS gene expression system has been used extensively, which operates eyes. By using system, genome-wide studies have resulted isolation functionally diverse groups Drosophila genes that interact disease proteins. We previously reported coexpressing Dikar by induced synthetic lethality. carried out follow-up experiments to isolate additional lethal alleles. Our data provide evidence lethality associated expressing is more common than thought be could escaped conventional genetic screens. results also suggest 1) leaky, allowing outside primary target eye types; 2) extremely cells; 3) combining leaky toxicity lethal-prone condition. Thus, modifications proteins’ acute frequently lead However, alleles are excluded from most screens, necessitating alternative approaches such as two-step method this study modifiers. Since reflects essential buffering networks, studying these may hold keys identify critical development pathways.