Reference: Tun NM, et al. (2013) Disulfide stress-induced aluminium toxicity: molecular insights through genome-wide screening of Saccharomyces cerevisiae. Metallomics 5(8):1068-75

Reference Help

Abstract


Formation of non-native disulfide bonds within or between proteins can lead to protein misfolding and disruption to cellular metabolism. Such a process is defined as disulfide stress. A marked effect of disulfide stress in cells is the elevated accumulation of the intracellular aluminium ion (Al(3+)) accompanied by increased cytotoxicity. To gain an in-depth understanding of the underlying molecular mechanism for disulfide stress-induced aluminium toxicity, the complete set of Saccharomyces cerevisiae deletion mutants (5047) was screened in this study simultaneously with a combination of the two stressors, diamide and Al(3+). The combined treatment of a benign concentration of diamide (0.8 mM) with a sublethal concentration of aluminium sulfate (0.4 mM) revealed 494 sensitive deletion mutants, distinct from those found when either of the single stressors (0.8 mM diamide or 0.4 mM aluminium sulfate) was used. Hierarchical clustering and functional analyses of the 494 mutants sensitive to the dual stressors indicated a significant enrichment in the genes involved in cell wall homeostasis, signaling cascades, secretory transport machinery and detoxification. The results highlight the process of maintaining cell wall integrity as the central response to the combined exposure of diamide and Al(3+), which is mediated by the signaling pathways and transcription activation via Rlm1p and Swi6p for biosynthesis of the essential cell wall components such as glucan and chitin. Sensitivity of mutants associated with endoplasmic reticulum (ER), vesicle and vacuole functions demonstrates that secretory machinery is essential for surviving the stress conditions, probably due to their roles in transporting polysaccharides to the cell wall and detoxification of accumulated Al(3+). Finally, the phenotype of 100 previously uncharacterized genes against the dual stressors will contribute to their eventual functional annotation.

Reference Type
Journal Article | Research Support, Non-U.S. Gov't
Authors
Tun NM, O'Doherty PJ, Perrone GG, Bailey TD, Kersaitis C, Wu MJ
Primary Lit For
Additional Lit For
Review For

Gene Ontology Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene/Complex Qualifier Gene Ontology Term Aspect Annotation Extension Evidence Method Source Assigned On Reference

Phenotype Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details.

Gene Phenotype Experiment Type Mutant Information Strain Background Chemical Details Reference

Disease Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene Disease Ontology Term Qualifier Evidence Method Source Assigned On Reference

Regulation Annotations


Increase the total number of rows displayed on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; to filter the table by a specific experiment type, type a keyword into the Filter box (for example, “microarray”); download this table as a .txt file using the Download button or click Analyze to further view and analyze the list of target genes using GO Term Finder, GO Slim Mapper, SPELL, or YeastMine.

Regulator Target Direction Regulation Of Happens During Method Evidence

Post-translational Modifications


Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through its pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Site Modification Modifier Reference

Interaction Annotations


Genetic Interactions

Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.

Interactor Interactor Allele Assay Annotation Action Phenotype SGA score P-value Source Reference

Physical Interactions

Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.

Interactor Interactor Assay Annotation Action Modification Source Reference

Functional Complementation Annotations


Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through its pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene Species Gene ID Strain background Direction Details Source Reference