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Genotoxic Stress Results in Selective P‐body Formation in S. cerevisiae
Author(s) -
Segal Scott P.,
Rathmann Blaine,
Koch Anthony,
Sutter Chad,
Michelson Cara,
Wilson Ted
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.692.1
Subject(s) - stress granule , nucleic acid , chemistry , oxidative stress , translation (biology) , dna damage , messenger rna , rna , dna , yeast , microbiology and biotechnology , biochemistry , saccharomyces cerevisiae , oxidizing agent , protein biosynthesis , gene , biology , organic chemistry
Survival mechanisms to cope with oxidative stress are conserved across all eukaryotes. However, our understanding of these mechanisms at the level of DNA and mRNA is poorly understood. Exposure to oxidizing agents can result in damage to lipids and nucleic acids, and can illicit a stress response. The genotoxic agent sodium dichromate oxidizes guanines resulting in formation of OxoG bases, or causes double strand breaks. In contrast, peroxides, allow for strong oxidation of lipids and nucleic acids. Control of translation may play a role as part of the DNA oxidative stress response. Upon exposing yeast to sodium dichromate, we saw a selective increase in P‐bodies, with a treatment as low as 15 uM, whereas stress granules fail to form. P‐bodies and stress granules are cytoplasmic structures in which non‐translating mRNA are found. Whereas P‐bodies contain RNA degradation factors, stress granules contain translation initiation factors. This suggests that stress granules contain stored RNA poised for translation. Moreover, the response occurs within 10 minutes of exposure, suggesting a model in which either damaged mRNA or mRNA transcribed from damaged genes is selectively degraded rather than stored. Currently, we are determining whether a co‐treatment with anti‐oxidants can abrogate this effect. This study provides novel insights into how yeast and perhaps other higher eukaryotic cells respond to DNA oxidation.