Functional Repurposing Revealed by Comparing S.聽pombe and S.聽cerevisiae Genetic Interactions
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Summary

We present a genetic interaction map of pairwise measures including 鈭?0%of nonessential S.聽pombe genes. By comparing interaction maps for fission and budding yeast, we confirmed widespread conservation of genetic relationships within and between complexes and pathways. However, we identified an important subset of orthologous complexes that have聽undergone functional 鈥渞epurposing鈥? the evolution of divergent functions and partnerships. We validated three functional repurposing events in S.聽pombe and mammalian cells and discovered that (1) two lumenal sensors of misfolded ER proteins, the kinase/nuclease Ire1 and the glucosyltransferase Gpt1, act together to mount an ER stress response; (2) ESCRT factors regulate spindle-pole-body duplication; and (3)聽a membrane-protein phosphatase and kinase complex, the STRIPAK complex, bridges the cis-Golgi, the centrosome, and the outer nuclear membrane to direct mitotic progression. Each discovery opens new areas of inquiry and鈥攖ogether鈥攈ave implications for model organism-based research and the evolution of genetic systems.

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