Base-substitution and frameshift mutagenesis by sodium chloride and potassium chloride in Saccharomyces cerevisiae

Parker, Kenneth; Borstel, R. C. von

doi:10.1016/0165-1218(87)90028-0

Cited by 19 publications

(7 citation statements)

References 9 publications

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“…presence or absence of Polζ or Ku). Several other types of environmental stress are mutagenic in yeast, in particular osmotic and DNA replication stresses [20], [21]. Both types of stress also activate the ESR, as evidenced by characteristic gene expression signatures and/or localization of Msn2 to the nucleus [1], [2], [31], [35].…”

Section: Resultsmentioning

confidence: 99%

“…One explanation of this phenomenon is that HSP90 can become “overtaxed”, such that its client proteins that function in chromosome segregation would interact with their targets in a misfolded, disfunctional state, with aberrant consequences for ploidy maintenance [6]. Other instances of genetic instability, in particular mutagenesis, were reported in response to chronic osmotic and DNA replication stresses [20], [21]. These types of stress are thought to be mutagenic at least in part because they can directly cause DNA damage: osmotic stress induces DNA breaks [22] and replication stress stalls DNA replication forks and creates regions of ssDNA [23].…”

Section: Introductionmentioning

confidence: 99%

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The Yeast Environmental Stress Response Regulates Mutagenesis Induced by Proteotoxic Stress

2013

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Yeast Environmental Stress Response Regulates Mutagenesis Induced by Proteotoxic Stress

2013

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“…In fact, anaerobiosis was shown to invoke a stress response in yeast cells [28], [29]. In addition, osmotic and DNA replication stress elicit mutagenesis [27], [30], [31]. Although the level of ROS is greatly reduced in anaerobic conditions and consequently the level of DNA damage generated, wild-type cells (as well as tsa1 Δ cells) could sense and respond to anoxia.…”

Section: Resultsmentioning

confidence: 99%

Loss of the Thioredoxin Reductase Trr1 Suppresses the Genomic Instability of Peroxiredoxin tsa1 Mutants

Ragu

Dardalhon²,

Sharma³

et al. 2014

PLoS ONE

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The absence of Tsa1, a key peroxiredoxin that scavenges H2O2 in Saccharomyces cerevisiae, causes the accumulation of a broad spectrum of mutations. Deletion of TSA1 also causes synthetic lethality in combination with mutations in RAD51 or several key genes involved in DNA double-strand break repair. In the present study, we propose that the accumulation of reactive oxygen species (ROS) is the primary cause of genome instability of tsa1Δ cells. In searching for spontaneous suppressors of synthetic lethality of tsa1Δ rad51Δ double mutants, we identified that the loss of thioredoxin reductase Trr1 rescues their viability. The trr1Δ mutant displayed a CanR mutation rate 5-fold lower than wild-type cells. Additional deletion of TRR1 in tsa1Δ mutant reduced substantially the CanR mutation rate of tsa1Δ strain (33-fold), and to a lesser extent, of rad51Δ strain (4-fold). Loss of Trr1 induced Yap1 nuclear accumulation and over-expression of a set of Yap1-regulated oxido-reductases with antioxidant properties that ultimately re-equilibrate intracellular redox environment, reducing substantially ROS-associated DNA damages. This trr1Δ -induced effect was largely thioredoxin-dependent, probably mediated by oxidized forms of thioredoxins, the primary substrates of Trr1. Thioredoxin Trx1 and Trx2 were constitutively and strongly oxidized in the absence of Trr1. In trx1Δ trx2Δ cells, Yap1 was only moderately activated; consistently, the trx1Δ trx2Δ double deletion failed to efficiently rescue the viability of tsa1Δ rad51Δ. Finally, we showed that modulation of the dNTP pool size also influences the formation of spontaneous mutation in trr1Δ and trx1Δ trx2Δ strains. We present a tentative model that helps to estimate the respective impact of ROS level and dNTP concentration in the generation of spontaneous mutations.

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“…Nevertheless, despite these similarities, there was no previous direct evidence tying high NaCl to cellular senescence. Also, many of the previous cell culture studies involved acute application of high NaCl for only a few hours 59,60,62 or used such high levels of NaCl that most cells died, leaving a small population that resumed proliferation with stable changes in karyotype. 63 In our present studies we tested whether levels of NaCl to which cells can adapt cause senescence.…”

Section: Discussionmentioning

confidence: 98%

High NaCl Promotes Cellular Senescence

Dmitrieva¹,

Burg²

2007

Cell Cycle

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High extracellular NaCl was previously shown to increase the number of DNA breaks in mammalian cells in tissue culture, renal medullary cells in vivo, C. elegans and marine invertebrates. It was also shown to increase reactive oxygen species in renal cells, resulting in oxidation of proteins and DNA. Cellular senescence is a common response to such damage. Therefore, in the present studies we looked for signs of senescence in cells exposed to high NaCl. We find that (1) the rate of proliferation of HeLa cells exposed to high NaCl decreases gradually to the point of arrest, and the cells display signs of senescence, including hypertrophy and increased auto fluorescence. (2) High NaCl accelerates the appearance of senescence in primary mouse embryonic fibroblasts, as measured by senescence-associated beta-galactosidase activity (SA-beta-gal). (3) High NaCl retards growth and markedly decreases the life span of C. elegans, accompanied by features of accelerated aging, such as decreased locomotion and increased number of SA-beta-gal positive cells. (4) Mouse renal medullary cells, which are normally continuously exposed to high NaCl, express increased p16(INK4) (another indicator of senescence) much earlier than do cells in the renal cortex, which has the same level of NaCl as peripheral blood. We conclude that high NaCl accelerates cellular senescence and aging, most likely secondary to the DNA breaks and oxidative damage that it causes.

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Base-substitution and frameshift mutagenesis by sodium chloride and potassium chloride in Saccharomyces cerevisiae

Cited by 19 publications

References 9 publications

The Yeast Environmental Stress Response Regulates Mutagenesis Induced by Proteotoxic Stress

The Yeast Environmental Stress Response Regulates Mutagenesis Induced by Proteotoxic Stress

Loss of the Thioredoxin Reductase Trr1 Suppresses the Genomic Instability of Peroxiredoxin tsa1 Mutants

High NaCl Promotes Cellular Senescence

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