Cell Cycle Sensing of Oxidative Stress in Saccharomyces cerevisiae by Oxidation of a Specific Cysteine Residue in the Transcription Factor Swi6p

Yeast cells begin to bud and enter the S phase when growth conditions are favorable during the G(1) phase. When subjected to some oxidative stresses, cells delay entry at G(1), allowing repair of cellular damage. Hence, oxidative stress sensing is coordinated with the regulation of cell cycle. We identified a novel function of the cell cycle regulator of Saccharomyces cerevisiae, Swi6p, as a redox sensor through its cysteine residue at position 404. When alanine was substituted at this position, the resultant mutant, C404A, was sensitive to several reactive oxygen species and oxidants including linoleic acid hydroperoxide, the superoxide anion, and diamide. This mutant lost the ability to arrest in G(1) phase upon treatment with lipid hydroperoxide. The Cys-404 residue of Swi6p in wild-type cells was oxidized to a sulfenic acid when cells were subjected to linoleic acid hydroperoxide. Mutation of Cys-404 to Ala abolished the down-regulation of expression of the G(1) cyclin genes CLN1, CLN2, PCL1, and PCL2 that occurred when cells of the wild type were exposed to the lipid hydroperoxide. In conclusion, oxidative stress signaling for cell cycle regulation occurs through oxidation of the G(1)/S-speicific transcription factor Swi6p and consequently leads to suppression of the expression of G(1) cyclins and a delay in cells entering the cell cycle.