The Yeast Environmental Stress Response Regulates Mutagenesis Induced by Proteotoxic Stress

Erika Shor, Catherine A. Fox, James R. Broach

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Conditions of chronic stress are associated with genetic instability in many organisms, but the roles of stress responses in mutagenesis have so far been elucidated only in bacteria. Here, we present data demonstrating that the environmental stress response (ESR) in yeast functions in mutagenesis induced by proteotoxic stress. We show that the drug canavanine causes proteotoxic stress, activates the ESR, and induces mutagenesis at several loci in an ESR-dependent manner. Canavanine-induced mutagenesis also involves translesion DNA polymerases Rev1 and Polζ and non-homologous end joining factor Ku. Furthermore, under conditions of chronic sub-lethal canavanine stress, deletions of Rev1, Polζ, and Ku-encoding genes exhibit genetic interactions with ESR mutants indicative of ESR regulating these mutagenic DNA repair processes. Analyses of mutagenesis induced by several different stresses showed that the ESR specifically modulates mutagenesis induced by proteotoxic stress. Together, these results document the first known example of an involvement of a eukaryotic stress response pathway in mutagenesis and have important implications for mechanisms of evolution, carcinogenesis, and emergence of drug-resistant pathogens and chemotherapy-resistant tumors.

Original languageEnglish (US)
Article numbere1003680
JournalPLoS genetics
Volume9
Issue number8
DOIs
StatePublished - Aug 1 2013

Fingerprint

environmental stress
mutagenesis
Mutagenesis
yeast
stress response
Yeasts
yeasts
Canavanine
canavanine
drug
chemotherapy
DNA
tumor
drugs
repair
DNA-Directed DNA Polymerase
DNA-directed DNA polymerase
DNA Repair
Pharmaceutical Preparations
pathogen

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

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The Yeast Environmental Stress Response Regulates Mutagenesis Induced by Proteotoxic Stress. / Shor, Erika; Fox, Catherine A.; Broach, James R.

In: PLoS genetics, Vol. 9, No. 8, e1003680, 01.08.2013.

Research output: Contribution to journalArticle

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