Systematic genetic array analysis links the Saccharomyces cerevisiae SAGA/SLIK and NuA4 component Tra1 to multiple cellular processes
| Autor: | Christopher J. Brandl, Julie Guzzo, Stephen M. T. Hoke, Brenda J. Andrews |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Cell signaling
Saccharomyces cerevisiae Proteins lcsh:QH426-470 Genetic Linkage Recombinant Fusion Proteins Saccharomyces cerevisiae Genes Fungal Green Fluorescent Proteins Biochemistry 03 medical and health sciences Gene Expression Regulation Fungal Genetics Transcriptional regulation Sorbitol Genetics(clinical) Kinase activity Gene Genetics (clinical) Alleles 030304 developmental biology Histone Acetyltransferases Oligonucleotide Array Sequence Analysis Sequence Deletion Cell Nucleus 0303 health sciences biology 030302 biochemistry & molecular biology Benzenesulfonates Systematic genetic array analysis Intracellular Membranes biology.organism_classification Staurosporine Phenotype Mitochondria SAGA complex lcsh:Genetics Protein Transport Trans-Activators Nuclear localization sequence Plasmids Research Article |
| Zdroj: | BMC Genetics BMC Genetics, Vol 9, Iss 1, p 46 (2008) Biochemistry Publications |
| ISSN: | 1471-2156 |
| Popis: | Background Tra1 is an essential 437-kDa component of the Saccharomyces cerevisiae SAGA/SLIK and NuA4 histone acetyltransferase complexes. It is a member of a group of key signaling molecules that share a carboxyl-terminal domain related to phosphatidylinositol-3-kinase but unlike many family members, it lacks kinase activity. To identify genetic interactions for TRA1 and provide insight into its function we have performed a systematic genetic array analysis (SGA) on tra1 SRR 3413, an allele that is defective in transcriptional regulation. Results The SGA analysis revealed 114 synthetic slow growth/lethal (SSL) interactions for tra1 SRR 3413. The interacting genes are involved in a range of cellular processes including gene expression, mitochondrial function, and membrane sorting/protein trafficking. In addition many of the genes have roles in the cellular response to stress. A hierarchal cluster analysis revealed that the pattern of SSL interactions for tra1 SRR 3413most closely resembles deletions of a group of regulatory GTPases required for membrane sorting/protein trafficking. Consistent with a role for Tra1 in cellular stress, the tra1 SRR 3413strain was sensitive to rapamycin. In addition, calcofluor white sensitivity of the strain was enhanced by the protein kinase inhibitor staurosporine, a phenotype shared with the Ada components of the SAGA/SLIK complex. Through analysis of a GFP-Tra1 fusion we show that Tra1 is principally localized to the nucleus. Conclusion We have demonstrated a genetic association of Tra1 with nuclear, mitochondrial and membrane processes. The identity of the SSL genes also connects Tra1 with cellular stress, a result confirmed by the sensitivity of the tra1 SRR 3413strain to a variety of stress conditions. Based upon the nuclear localization of GFP-Tra1 and the finding that deletion of the Ada components of the SAGA complex result in similar phenotypes as tra1 SRR 3413, we suggest that the effects of tra1 SRR 3413are mediated, at least in part, through its role in the SAGA complex. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|