Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 2722K) PDF+supp data (3530K) PPT slides of all figures Supplemental Material Related biobytes podcast Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Google Scholar Articles by Madia, F. Articles by Longo, V. D. PubMed PubMed Citation Articles by Madia, F. Articles by Longo, V. D. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Compound via MeSH Substance via MeSH Social Bookmarking                            What's this?

Oncogene homologue Sch9 promotes age-dependent mutations by a superoxide and Rev1/Pol-dependent mechanism

¹ Andrus Gerontology Center and Department of Biological Sciences, and ² Molecular and Computational Biology, Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089

Correspondence to Valter D. Longo: vlongo{at}usc.edu

Oncogenes contribute to tumorigenesis by promoting growth and inhibiting apoptosis. Here we examine the function of Sch9, the Saccharomyces cerevisiae homologue of the mammalian Akt and S6 kinase, in DNA damage and genomic instability during aging in nondividing cells. Attenuation of age-dependent increases in base substitutions, small DNA insertions/deletions, and gross chromosomal rearrangements (GCRs) in sch9 mutants is associated with increased mitochondrial superoxide dismutase (MnSOD) expression, decreased DNA oxidation, reduced REV1 expression and translesion synthesis, and elevated resistance to oxidative stress-induced mutagenesis. Deletion of REV1, the lack of components of the error-prone Pol, or the overexpression of SOD1 or SOD2 is sufficient to reduce age-dependent point mutations in SCH9 overexpressors, but REV1 deficiency causes a major increase in GCRs. These results suggest that the proto-oncogene homologue Sch9 promotes the accumulation of superoxide-dependent DNA damage in nondividing cells, which induces error-prone DNA repair that generates point mutations to avoid GCRs and cell death during the first round of replication.

Abbreviations used in this paper: 5FOA, 5-fluoroorotic acid; 8-OHdG, 8-hydroxy-2'deoxyguanidine; ANOVA, analysis of variance; CFU, colony-forming unit; GCR, gross chromosomal rearrangement; IGF-I, insulin-like growth factor 1; MMS, methyl methane sulfonate; SDC, synthetic dextrose complete; SOD, superoxide dismutase; TLS, translesion synthesis.

© 2009 Madia et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

CiteULike

Complore

Connotea

Del.icio.us

Digg

Facebook

Reddit

Technorati

Twitter

This article has been cited by other articles:

• Ge, H., Wei, M., Fabrizio, P., Hu, J., Cheng, C., Longo, V. D., Li, L. M. (2009). Comparative analyses of time-course gene expression profiles of the long-lived sch9{Delta} mutant. Nucleic Acids Res 0: gkp849v1-gkp849 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents