NARAYANAN, SIDDHARTH (2011) CROSSTALK BETWEEN THE ER STRESS PATHWAY AND OSMOTIC STRESS IN S. CEREVISIAE. Doctoral thesis, Durham University.
|PDF (PhD thesis) - Accepted Version|
In Saccharomyces cerevisiae, the general stress response (GSR) protects cells from diverse stress conditions such as osmotic stress and heat stress, while the Unfolded Protein Response (UPR) is a protein folding stress signalling pathway which maintains homeostasis of the endoplasmic reticulum (ER). A mechanism of how and if at all the UPR integrates with other pathways is largely unknown. The focus of this thesis was to determine whether essential components of the UPR like the bZIP transcription factor Hac1p and the Rpd3p-Sin3p histone deacetylase integrated within osmotic stress and to identify a possible mechanism of such an integration event.
Data from this thesis demonstrate that UPR components protect cells from hyperosmotic stress. Hac1p is a direct positive regulator of GSR genes. Rpd3p and Hac1p belong to the same pathway in activating GSR genes. Data also suggest that Hac1p does not contribute to the increase in nucleosomal histone acetylation levels after osmotic stress. The Gcn5 histone acetyltransferase contributes to the increase in histone acetylation observed after osmotic stress. The Rpd3p represses GSR genes in unstressed cells but also contributes to the activation of GSR genes after hyperosmotic shock. The Rpd3 large complex and not the small complex is involved regulating GSR gene expression. Subsequent investigation demonstrates that a possible mechanism by which the UPR contributes to the GSR gene activation is by the RNA polymerase II clearance at the GSR gene promoters.
|Item Type:||Thesis (Doctoral)|
|Award:||Doctor of Philosophy|
|Keywords:||ER stress, osmotic stress, Hac1 bZIP, Rpd3 histone deacetylase, signal transduction|
|Faculty and Department:||Faculty of Science > Biological and Biomedical Sciences, School of|
|Copyright:||Copyright of this thesis is held by the author|
|Deposited On:||16 Mar 2012 10:05|