TY - JOUR

T1 - Analysis of beta-1,3-glucan assembly in Saccharomyces cerevisiae using a synthetic interaction network and altered sensitivity to caspofungin

AU - Lesage, Guillaume

AU - Sdicu, Anne-Marie

AU - Ménard, Patrice

AU - Shapiro, Jesse

AU - Hussein, Shamiza

AU - Bussey, Howard

N1 - Keywords: Antifungal Agents; Biochemistry; Biological Transport; Cell Cycle; Cell Survival; Cell Wall; Chitin; Cytoskeleton; Dose-Response Relationship, Drug; Drug Resistance, Fungal; Drug Resistance, Multiple; Echinocandins; Gene Deletion; Genes, Fungal; Genotype; Glucans; Glucosyltransferases; Haploidy; Ions; Membrane Glycoproteins; Membrane Proteins; Models, Biological; Mutation; Oligonucleotide Array Sequence Analysis; Peptides, Cyclic; Phenotype; Protein Binding; Proteins; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Signal Transduction; Time Factors; Transcription Factors; Transcription, Genetic; Ubiquitin; beta-Glucans

PY - 2004

Y1 - 2004

N2 - Large-scale screening of genetic and chemical-genetic interactions was used to examine the assembly and regulation of beta-1,3-glucan in Saccharomyces cerevisiae. Using the set of deletion mutants in approximately 4600 nonessential genes, we scored synthetic interactions with genes encoding subunits of the beta-1,3-glucan synthase (FKS1, FKS2), the glucan synthesis regulator (SMI1/KNR4), and a beta-1,3-glucanosyltransferase (GAS1). In the resulting network, FKS1, FKS2, GAS1, and SMI1 are connected to 135 genes in 195 interactions, with 26 of these genes also interacting with CHS3 encoding chitin synthase III. A network core of 51 genes is multiply connected with 112 interactions. Thirty-two of these core genes are known to be involved in cell wall assembly and polarized growth, and 8 genes of unknown function are candidates for involvement in these processes. In parallel, we screened the yeast deletion mutant collection for altered sensitivity to the glucan synthase inhibitor, caspofungin. Deletions in 52 genes led to caspofungin hypersensitivity and those in 39 genes to resistance. Integration of the glucan interaction network with the caspofungin data indicates an overlapping set of genes involved in FKS2 regulation, compensatory chitin synthesis, protein mannosylation, and the PKC1-dependent cell integrity pathway.

AB - Large-scale screening of genetic and chemical-genetic interactions was used to examine the assembly and regulation of beta-1,3-glucan in Saccharomyces cerevisiae. Using the set of deletion mutants in approximately 4600 nonessential genes, we scored synthetic interactions with genes encoding subunits of the beta-1,3-glucan synthase (FKS1, FKS2), the glucan synthesis regulator (SMI1/KNR4), and a beta-1,3-glucanosyltransferase (GAS1). In the resulting network, FKS1, FKS2, GAS1, and SMI1 are connected to 135 genes in 195 interactions, with 26 of these genes also interacting with CHS3 encoding chitin synthase III. A network core of 51 genes is multiply connected with 112 interactions. Thirty-two of these core genes are known to be involved in cell wall assembly and polarized growth, and 8 genes of unknown function are candidates for involvement in these processes. In parallel, we screened the yeast deletion mutant collection for altered sensitivity to the glucan synthase inhibitor, caspofungin. Deletions in 52 genes led to caspofungin hypersensitivity and those in 39 genes to resistance. Integration of the glucan interaction network with the caspofungin data indicates an overlapping set of genes involved in FKS2 regulation, compensatory chitin synthesis, protein mannosylation, and the PKC1-dependent cell integrity pathway.

M3 - Journal article

C2 - 15166135

VL - 167

SP - 35

EP - 49

JO - Genetics

JF - Genetics

SN - 1943-2631

IS - 1

ER -