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Reversible protein phosphorylation is a signaling mechanism involved in all cellular processes. To create a systems view of the signaling apparatus in budding yeast, we generated an epistatic miniarray profile (E-MAP) comprised of 100,000 pairwise, quantitative genetic interactions, including virtually all protein and small-molecule kinases and phosphatases as well as key cellular regulators. Quantitative genetic interaction mapping reveals factors working in compensatory pathways (negative genetic interactions) or those operating in linear pathways (positive genetic interactions). We found an enrichment of positive genetic interactions between kinases, phosphatases, and their substrates. In addition, we assembled a higher-order map from sets of three genes that display strong interactions with one another: triplets enriched for functional connectivity. The resulting network view provides insights into signaling pathway regulation and reveals a link between the cell-cycle kinase, Cak1, the Fus3 MAP kinase, and a pathway that regulates chromatin integrity during transcription by RNA polymerase II.
Pubmed ID: 19269370 RIS Download
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This database currently holds E-MAP scores (individual interactions and correlation coefficients) for budding yeast genes involved in the early secretory pathway and chromosome function (including DNA damage and repair, transcriptional control, chromosome segregation and telomere regulation). E-MAPs (Epistatic Mini Array Profiles) are formed by creating and quantifying high-density genetic interaction maps. With this method, observed double mutant colony sizes are compared to those that would be expected from a distribution of typical double mutant colonies of each strain. Each interaction is assigned a score, which indicates the magnitude of the difference from the expected value and the certainty of the score. Negative (or aggravating) scores (< -2.5) correspond to synthetic sick/lethal interactions while positive (or alleviating) scores (> +2.5) corresponds to epistatic or suppressor interactions.
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