title: Differential genetic interactions of yeast stress response MAPK pathways.
abstract: Genetic interaction screens have been applied with great success in several organisms to study gene function and the genetic architecture of the cell. However, most studies have been performed under optimal growth conditions even though many functional interactions are known to occur under specific cellular conditions. In this study, we have performed a large-scale genetic interaction analysis in Saccharomyces cerevisiae involving approximately 49 × 1,200 double mutants in the presence of five different stress conditions, including osmotic, oxidative and cell wall-altering stresses. This resulted in the generation of a differential E-MAP (or dE-MAP) comprising over 250,000 measurements of conditional interactions. We found an extensive number of conditional genetic interactions that recapitulate known stress-specific functional associations. Furthermore, we have also uncovered previously unrecognized roles involving the phosphatase regulator Bud14, the histone methylation complex COMPASS and membrane trafficking complexes in modulating the cell wall integrity pathway. Finally, the osmotic stress differential genetic interactions showed enrichment for genes coding for proteins with conditional changes in phosphorylation but not for genes with conditional changes in gene expression. This suggests that conditional genetic interactions are a powerful tool to dissect the functional importance of the different response mechanisms of the cell.
authors.affiliation: Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid and Instituto Ramón y Cajal de Investigaciones Sanitarias (IRYCIS), Madrid, Spain.
authors.forename: Humberto
authors.initials: H
authors.lastname: Martin
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Shales
authors.affiliation: Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid and Instituto Ramón y Cajal de Investigaciones Sanitarias (IRYCIS), Madrid, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Fernandez-Piñar
authors.affiliation: Center for Quantitative Biology and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wei
authors.affiliation: Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid and Instituto Ramón y Cajal de Investigaciones Sanitarias (IRYCIS), Madrid, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Molina
authors.affiliation: Department of Chemistry, Princeton University, Princeton, NJ, USA.
authors.forename: Dorothea
authors.initials: D
authors.lastname: Fiedler
authors.affiliation: Chemistry and Chemical Biology Graduate Program, University of California, San Francisco, CA, USA.
authors.forename: Kevan M
authors.initials: KM
authors.lastname: Shokat
authors.affiliation: European Molecular Biology Laboratory, European Bioinformatics Institute, Cambridge, UK iBiMED and Department of Health Sciences, University of Aveiro, Aveiro, Portugal pbeltrao@ebi.ac.uk nevan.krogan@ucsf.edu.
authors.forename: Pedro
authors.initials: P
authors.lastname: Beltrao
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA USA Howard Hughes Medical Institute, University of California, San Francisco, CA, USA Center for Systems and Synthetic Biology, University of California, San Francisco, CA, USA.
authors.forename: Wendell
authors.initials: W
authors.lastname: Lim
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA USA Center for Systems and Synthetic Biology, University of California, San Francisco, CA, USA California Institute for Quantitative Biosciences, QB3, San Francisco, CA, USA J. David Gladstone Institutes, San Francisco, CA, USA pbeltrao@ebi.ac.uk nevan.krogan@ucsf.edu.
authors.forename: Nevan J
authors.initials: NJ
authors.lastname: Krogan
mesh_terms: D002473:Cell Wall; D015966:Gene Expression Regulation, Fungal; D053263:Gene Regulatory Networks; D005800:Genes, Fungal; D020935:MAP Kinase Signaling System / Q000235:genetics*; D053858:Metabolic Networks and Pathways / Q000235:genetics; D009154:Mutation; D009997:Osmotic Pressure; D018384:Oxidative Stress / Q000235:genetics; D010957:Plasmids; D021381:Protein Transport / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000502:physiology; D013312:Stress, Physiological / Q000235:genetics*
chemical_list: D029701:Saccharomyces cerevisiae Proteins
keywords: cell wall integrity; genetic interactions; osmotic shock; stress response