title: Role of RAS2 in recovery from chronic stress: effect on yeast life span.
abstract: The replicative life span of Saccharomyces cerevisiae was previously shown to be modulated by the homologous signal transducers Ras1p and Ras2p in a reciprocal manner. We have used thermal stress as a life span modulator in order to uncover functional differences between the RAS genes that may contribute to their divergent effects on life span. Chronic exposure of cells throughout life to recurring heat shocks at sublethal temperatures decreased their replicative life span. ras2 mutants, however, suffered the largest decrease compared to wild-type and ras1 mutant cells. The decrease was correlated with a substantial delay in resumption of budding upon recovery from these heat shocks, indicating an impaired renewal of cell cycling. Detailed analysis of gene expression showed that, during recovery, ras2 mutants were selectively impaired in down-regulation of stress-responsive genes and up-regulation of growth-promoting genes. Our results suggest that one of the functions of RAS2 in maintaining life span, for which RAS1 does not substitute, is to ensure renewal of growth and cell division after bouts of stress that cells encounter during their life. This activity of RAS2 is effected by the cyclic AMP pathway. Overexpression of RAS2, but not RAS2(ser42) which is deficient in the activation of adenylate cyclase, completely reversed the effect of chronic stress on life span. Thus, RAS2 is limiting for longevity in the face of chronic stress. Since RAS2 is known to down-regulate stress responses, this demonstrates that for longevity the ability to recover from stress is at least as important as the ability to mount a stress response.
authors.affiliation: Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, New Orleans, Louisiana, 70112, USA.
authors.forename: S
authors.initials: S
authors.lastname: Shama
authors.forename: P A
authors.initials: PA
authors.lastname: Kirchman
authors.forename: J C
authors.initials: JC
authors.lastname: Jiang
authors.forename: S M
authors.initials: SM
authors.lastname: Jazwinski
mesh_terms: D015152:Blotting, Northern; D015153:Blotting, Western; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology; D015536:Down-Regulation; D005656:Fungal Proteins; D017353:Gene Deletion; D015870:Gene Expression; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal / Q000235:genetics; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018869:Heat-Shock Response / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D013696:Temperature; D015854:Up-Regulation; D018631:ras Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D005656:Fungal Proteins; D006360:Heat-Shock Proteins; D029701:Saccharomyces cerevisiae Proteins; C070972:HsP104 protein, S cerevisiae; D000242:Cyclic AMP; C489014:RAS1 protein, S cerevisiae; C489015:RAS2 protein, S cerevisiae; D018631:ras Proteins