Translational Repression Mediated By the Genotoxic Agent Sodium Dichromate Results in P‐body Formation in S. cerevisiae

Abstract

Mechanisms to cope with oxidative stress are conserved across eukaryotes. For instance, exposure to oxidation can result in lipid and nucleic acid damage and elicit a stress response. The genotoxic agent, sodium dichromate oxidizes guanines resulting in OxoG bases, induces double strand breaks, or generates abasic sites. Therefore, an oxidative stress response is crucial to maintain proper cellular function. In response to stress, cells control gene expression by repressing translation. Repressed mRNA may localize to P‐bodies or stress granules; cytoplasmic structures where non‐translating mRNA are found. While P‐bodies contain mRNA degradation factors, stress granules contain translation initiation factors, allowing for storage of mRNA until removal of the stress.Exposure of yeast to sodium dichromate caused an increase in P‐bodies, whereas stress granules failed to form. The response occurs within 10 min. of exposure and is dependent on translational repression. Interestingly, use of the antioxidant, quercetin, abrogated the increase in P‐body formation during co‐treatment with sodium dichromate. Our data suggests a model in which damaged mRNA or mRNA transcribed from damaged genes are degraded rather than stored. We suspect oxidative damage may halt translating ribosomes on these mRNA, activating the no‐go decay pathway.