Loss of nonsense mediated decay suppresses mutations in Saccharomyces cerevisiae TRA1
| العنوان: | Loss of nonsense mediated decay suppresses mutations in Saccharomyces cerevisiae TRA1 |
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| المؤلفون: | Stephanie Kvas, Christopher J. Brandl, Gregory B. Gloor |
| المصدر: | BMC Genetics BMC Genetics, Vol 13, Iss 1, p 19 (2012) |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Saccharomyces cerevisiae Proteins, lcsh:QH426-470, DNA repair, Nonsense-mediated decay, Saccharomyces cerevisiae, Biology, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Gene Expression Regulation, Fungal, medicine, Genetics, Genetics(clinical), Genes, Suppressor, Gene, Genetics (clinical), 030304 developmental biology, Histone Acetyltransferases, Sequence Deletion, Regulation of gene expression, 0303 health sciences, Mutation, Ethanol, Nonsense mediated decay, biology.organism_classification, Phenotype, Tra1, Yeast, Complementation, lcsh:Genetics, Upf1, Gene expression, 030217 neurology & neurosurgery, Second-site suppression, Research Article |
| الوصف: | BackgroundTra1 is an essential protein inSaccharomyces cerevisiae. It was first identified in the SAGA and NuA4 complexes, both with functions in multiple aspects of gene regulation and DNA repair, and recently found in the ASTRA complex. Tra1 belongs to the PIKK family of proteins with a C-terminal PI3K domain followed by a FATC domain. Previously we found that mutation of leucine to alanine at position 3733 in the FATC domain of Tra1 (tra1-L3733A) results in transcriptional changes and slow growth under conditions of stress. To further define the regulatory interactions of Tra1 we isolated extragenic suppressors of thetra1-L3733Aallele.ResultsWe screened for suppressors of the ethanol sensitivity caused bytra1-L3733A. Eleven extragenic recessive mutations, belonging to three complementation groups, were identified that partially suppressed a subset of the phenotypes caused by tra1-L3733A. Using whole genome sequencing we identified one of the mutations as an opal mutation at tryptophan 165 ofUPF1/NAM7. Partial suppression of the transcriptional defect resulting fromtra1-L3733Awas observed atGAL10, but not atPHO5. Suppression was due to loss of nonsense mediated decay (NMD) since deletion of any one of the three NMD surveillance components (upf1/nam7, upf2/nmd2, orupf3) mediated the effect. Deletion ofupf1suppressed a second FATC domain mutation,tra1-F3744A, as well as a mutation to the PIK3 domain. In contrast, deletions of SAGA or NuA4 components were not suppressed.ConclusionsWe have demonstrated a genetic interaction betweenTRA1and genes of the NMD pathway. The suppression is specific for mutations inTRA1. Since NMD and Tra1 generally act reciprocally to control gene expression, and the FATC domain mutations do not directly affect NMD, we suggest that suppression occurs as the result of overlap and/or crosstalk in these two broad regulatory networks. |
| تدمد: | 1471-2156 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::60e0aa17bb7f06f773835744d6ab77afTest https://pubmed.ncbi.nlm.nih.gov/22439631Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....60e0aa17bb7f06f773835744d6ab77af |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14712156 |
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