Original Research ARTICLE
Functional genomics indicates yeast requires Golgi/ER transport, chromatin remodeling, and DNA repair for low dose DMSO tolerance
- Department of Nutritional Science and Toxicology, University of California, Berkeley, CA, USA
Dimethyl sulfoxide (DMSO) is frequently utilized as a solvent in toxicological and pharmaceutical investigations. It is therefore important to establish the cellular and molecular targets of DMSO in order to differentiate its intrinsic effects from those elicited by a compound of interest. We performed a genome-wide functional screen in Saccharomyces cerevisiae to identify deletion mutants exhibiting sensitivity to 1% DMSO, a concentration standard to yeast chemical profiling studies. We report that mutants defective in Golgi/ER transport are sensitive to DMSO, including those lacking components of the conserved oligomeric Golgi (COG) complex. Moreover, strains deleted for members of the SWR1 histone exchange complex are hypersensitive to DMSO, with additional chromatin remodeling mutants displaying a range of growth defects. We also identify DNA repair genes important for DMSO tolerance. Finally, we demonstrate that overexpression of histone H2A.Z, which replaces chromatin-associated histone H2A in a SWR1-catalyzed reaction, confers resistance to DMSO. Many yeast genes described in this study have homologs in more complex organisms, and the data provided is applicable to future investigations into the cellular and molecular mechanisms of DMSO toxicity.
Keywords: DMSO, dimethyl sulfoxide, functional genomics, functional profiling, yeast, chromatin
Citation: Gaytán BD, Loguinov AV, De La Rosa VY, Lerot J-M and Vulpe CD (2013) Functional genomics indicates yeast requires Golgi/ER transport, chromatin remodeling, and DNA repair for low dose DMSO tolerance. Front. Genet. 4:154. doi: 10.3389/fgene.2013.00154
Received: 18 June 2013; Paper pending published: 12 July 2013;
Accepted: 24 July 2013; Published online: 13 August 2013.
Edited by:Michael Aschner, Vanderbilt University Medical Center, USA
Reviewed by:Jonathan Freedman, National Institute of Environmental Health Science, USA
Nallasivam Palanisamy, University of Michigan, USA
Copyright © 2013 Gaytán, Loguinov, De La Rosa, Lerot and Vulpe. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Chris D. Vulpe, Department of Nutritional Science and Toxicology, University of California, Berkeley, 317 Morgan Hall, Berkeley, CA 94720, USA e-mail: firstname.lastname@example.org