A single gene change can extend yeast life span: the role of Ras in cellular senescence.
The budding yeast Saccharomyces cerevisiae has a limited life span (reproductive capacity), which is measured by the number of times an individual cell divides. There is evidence for the involvement of a senescence factor that affects cell cycle traversal in older yeast cells. Distinct alterations in the abundance of a handful of transcripts have been identified during the life span of this organism, and the genes that specify these mRNAs have been cloned. This raises the question whether the activity of one or more genes can alter the yeast life span. Indeed, the controlled expression of the transforming gene of Harvey murine sarcoma virus (v-Ha-ras) was found to extend the life span nearly two-fold. The normal homologs of this oncogene, RAS1 and RAS2, play a central role in the integration of cell growth and the cell cycle in yeast. Expression of v-Ha-ras appears to impinge on this integration. We suggest that it is the relative levels of the senescence factor and the Ras protein that determine whether a cell ceases to divide and senesces. We liken the senescence factor to the product of an anti-oncogene or tumor suppressor gene that neutralizes Ras.
Jazwinski
S M
SM
Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, New Orleans 70112.
Chen
J B
JB
Sun
J
J
D002453:Cell Cycle / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D016922:Cellular Senescence; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005800:Genes, Fungal; D011905:Genes, ras; D005816:Genetic Complementation Test; D015689:Oncogene Protein p21(ras) / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D013997:Time Factors; D018631:ras Proteins
D005656:Fungal Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D019204:GTP-Binding Proteins; D015689:Oncogene Protein p21(ras); C489014:RAS1 protein, S cerevisiae; C489015:RAS2 protein, S cerevisiae; D018631:ras Proteins