Methylmethane Sulfonate Increases the Level of Superoxide Anions in Yeast Cells

ABSTRACT

Ty1 is a Saccharomyces cerevisiae retrotransposon with life cycle and structure very similar to the known oncoviruses. The transposition of the Ty1 mobile genetic element is induced by different stress conditions and chemical agents. Mutagens and carcinogens activate Ty1 elements for retrotransposition by certain types of genome injuries through DNA-damage signaling pathways but the mechanism of transcriptional activation by DNA damage has not been enough elucidated. Many of the activators of Ty1 mobility are powerful inducers of oxidative stress. Reactive oxygen species (ROS) can generate a variety of DNA lesions and can lead to a significant activation of Ty1 mobility. Recent data indicate that treatment of S. cerevisiae cells with the Ty1-mobility inducer methylmethane sulfonate (MMS) results in increased ROS levels. In response to MMS, both a direct DNA damaging effect and an enhanced ROS levels play role in the activation of Ty retrotransposition. The results obtained in this study provide evidence for a dependence of Ty1 retrotranspsoition on increased production of ROS. The increased ROS levels may have an independent and a key role in the induction of Ty1 retrotransposition by MMS. We suppose that MMS treatment of cells with functioning mitochondrial oxidative phosphorylation induces Ty1 retrotransposition by both, increased ROS levels and direct DNA damages, and the increased ROS levels seems to have the major role in the induction of Ty1 mobility.

Keyword:

• DNA-damage
• Reactive oxygen species
• Saccharomyces cerevisiae
• Ty1 retrotransposon