Comparative Genomic Screen in Two Yeasts Reveals Conserved Pathways in the Response Network to Phenol Stress

• Main Authors: Bashar Alhoch, Alan Chen, Elaine Chan, Asmaa Elkabti, Sasha Fariña, Catherine Gilbert, Jean Kang, Bradley King, Karen Leung, Julia Levy, Elizabeth Martin, Benjamin Mazer, Sara McKinney, Alexandra Moyzis, Margaret Nurimba, Michelle Ozaki, Kathleen Purvis-Roberts, Joshua Marc Rothman, Shravya Raju, Cynthia Selassie, Oliver Smith, Julia Ticus, Gretchen Edwalds-Gilbert, M. Cristina Negritto, Ruye Wang, Zhaohua Tang
• Format: Article
• Language: English
• Published: Oxford University Press 2019-03-01
• Series: G3: Genes, Genomes, Genetics
• Subjects: comparative genomic screen; phenol stress response in yeasts; cell cycle regulation and DNA repair; ergosterol and V-ATPase; UPR
• Online Access: http://g3journal.org/lookup/doi/10.1534/g3.118.201000

Living organisms encounter various perturbations, and response mechanisms to such perturbations are vital for species survival. Defective stress responses are implicated in many human diseases including cancer and neurodegenerative disorders. Phenol derivatives, naturally occurring and synthetic, display beneficial as well as detrimental effects. The phenol derivatives in this study, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and bisphenol A (BPA), are widely used as food preservatives and industrial chemicals. Conflicting results have been reported regarding their biological activity and correlation with disease development; understanding the molecular basis of phenol action is a key step for addressing issues relevant to human health. This work presents the first comparative genomic analysis of the genetic networks for phenol stress response in an evolutionary context of two divergent yeasts, Schizosaccharomyces pombe and Saccharomyces cerevisiae. Genomic screening of deletion strain libraries of the two yeasts identified genes required for cellular response to phenol stress, which are enriched in human orthologs. Functional analysis of these genes uncovered the major signaling pathways involved. The results provide a global view of the biological events constituting the defense process, including cell cycle arrest, DNA repair, phenol detoxification by V-ATPases, reactive oxygen species alleviation, and endoplasmic reticulum stress relief through ergosterol and the unfolded protein response, revealing novel roles for these cellular pathways.