title: Modulation of the yeast protein interactome in response to DNA damage.
abstract: Cells deploy diverse mechanisms to physiologically adapt to potentially detrimental perturbations. These mechanisms include changes in the organization of protein-protein interaction networks (PINs). Most PINs characterized to date are portrayed in a single environmental condition and are thus likely to miss important connections among biological processes. In this report, we show that the yeast DHFR-PCA on high-density arrays allows to detects modulations of protein-protein interactions (PPIs) in different conditions by testing more than 1000 PPIs in standard and in a drug-inducing DNA damage conditions. We identify 156 PPIs that show significant modulation in response to DNA damage. We provide evidence that modulated PPIs involve essential genes (NOP7, EXO84 and LAS17) playing critical roles in response to DNA damage. Additionally, we show that a significant proportion of PPI changes are likely explained by changes in protein localization and, to a lesser extent, protein abundance. The protein interaction modules affected by changing PPIs support the role of mRNA stability and translation, protein degradation and ubiquitylation and the regulation of the actin cytoskeleton in response to DNA damage. Overall, we provide a valuable tool and dataset for the study of the rewiring of PINs in response to environmental perturbations.
  
  
  CONCLUSIONS
  We show that the DHFR-PCA is a high-throughput method that allows the detection of changes in PPIs associated with different environmental conditions using DNA damage response as a testbed. We provide a valuable resource for the study of DNA damage in eukaryotic cells. This article is part of a Special Issue: Can Proteomics Fill the Gap Between Genomics and Phenotypes?
authors.affiliation: Département de Biologie, PROTEO and Institut de Biologie Intégrative et des Systèmes, Université Laval, Québec, Québec G1V 0A6, Canada.
authors.forename: Samuel
authors.initials: S
authors.lastname: Rochette
authors.affiliation: Département de Biologie, PROTEO and Institut de Biologie Intégrative et des Systèmes, Université Laval, Québec, Québec G1V 0A6, Canada.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Gagnon-Arsenault
authors.affiliation: Département de Biologie, PROTEO and Institut de Biologie Intégrative et des Systèmes, Université Laval, Québec, Québec G1V 0A6, Canada.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Diss
authors.affiliation: Département de Biologie, PROTEO and Institut de Biologie Intégrative et des Systèmes, Université Laval, Québec, Québec G1V 0A6, Canada. Electronic address: Christian.landry@bio.ulaval.ca.
authors.forename: Christian R
authors.initials: CR
authors.lastname: Landry
mesh_terms: D004249:DNA Damage; D008727:Methotrexate / Q000494:pharmacology; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D060066:Protein Interaction Maps / Q000235:genetics; D012331:RNA, Fungal / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*
chemical_list: D012331:RNA, Fungal; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D008741:Methyl Methanesulfonate; D013762:Tetrahydrofolate Dehydrogenase; D008727:Methotrexate
keywords: DNA damage; MMS; P-bodies; Protein interaction network; Protein-fragment complementation assay; Yeast