Genetic effects of formaldehyde in yeast. I. Influence of the growth stages on killing and recombination

Chanet, Roland; Izard, C; Moustacchi, E.

doi:10.1016/0027-5107(75)90193-1

Cited by 30 publications

(5 citation statements)

References 17 publications

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“…The strongly inhibitory effect of 1 can be attributed to its ability to form adducts with biomolecules, which can result in cross-links between, for example, DNA and protein or between different DNA molecules. − Exposure of yeast to 1 was found to involve induction of 622 and repression of 610 open-reading frames . Yasokawa et al concluded that proteins appear to be the major target of the inhibitory mechanism of 1 .…”

Section: Resultsmentioning

confidence: 99%

Identification of Small Aliphatic Aldehydes in Pretreated Lignocellulosic Feedstocks and Evaluation of Their Inhibitory Effects on Yeast

Cavka

Stagge

Jönsson

2015

J. Agric. Food Chem.

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Six lignocellulosic hydrolysates produced through acid pretreatment were analyzed for the occurrence of formaldehyde, acetaldehyde, and glycolaldehyde. Acetaldehyde was found in all six (0.3-1.6 mM) and formaldehyde in four (≤ 4.4 mM), whereas glycolaldehyde was not detected. To assess the relevance of these findings, fermentations with yeast and formaldehyde or acetaldehyde were performed in the concentration interval 0.5-10 mM. Formaldehyde already inhibited at 1.0 mM, whereas 5.0 mM acetaldehyde was needed to obtain a clear inhibitory effect. After 24 h of fermentation, 1.5 mM formaldehyde reduced the glucose consumption by 85%, the balanced ethanol yield by 92%, and the volumetric productivity by 91%. The results show that formaldehyde and acetaldehyde are prevalent in pretreated lignocellulose and that formaldehyde in some cases could explain a large part of the inhibitory effects on yeast by lignocellulosic hydrolysates, as three of six hydrolysates contained ≥ 1.9 mM formaldehyde, which was shown to be strongly inhibitory.

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Section: Resultsmentioning

confidence: 99%

Identification of Small Aliphatic Aldehydes in Pretreated Lignocellulosic Feedstocks and Evaluation of Their Inhibitory Effects on Yeast

Cavka

Stagge

Jönsson

2015

J. Agric. Food Chem.

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“…In general, the investigations by other groups contrast with ours in that we employed quantitative and sensitive measures of toxicity (i.e., growth inhibition) at doses closer to environmental exposure (0.6 mM or less), considering endogenous levels of FA in human blood and tissue range from approximately 0.08–0.4 mM (Andersen et al, 2010; Heck and Casanova, 2004; National Toxicology Program (NTP), 2010). Initial studies of FA toxicity in yeast found high concentrations of FA (17–83 mM) increase recombination (Chanet et al, 1975), alter excision repair mutant survival (Chanet et al, 1976), and generate DNA-protein crosslinks (Magana-Schwencke and Ekert, 1978). Although these analyses utilized much higher doses, the results are generally congruent to ours.…”

Section: Discussionmentioning

confidence: 99%

Functional Toxicogenomic Profiling Expands Insight into Modulators of Formaldehyde Toxicity in Yeast

et al. 2016

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Formaldehyde (FA) is a commercially important chemical with numerous and diverse uses. Accordingly, occupational and environmental exposure to FA is prevalent worldwide. Various adverse effects, including nasopharyngeal, sinonasal, and lymphohematopoietic cancers, have been linked to FA exposure, prompting designation of FA as a human carcinogen by U.S. and international scientific entities. Although the mechanism(s) of FA toxicity have been well studied, additional insight is needed in regard to the genetic requirements for FA tolerance. In this study, a functional toxicogenomics approach was utilized in the model eukaryotic yeast Saccharomyces cerevisiae to identify genes and cellular processes modulating the cellular toxicity of FA. Our results demonstrate mutant strains deficient in multiple DNA repair pathways–including homologous recombination, single strand annealing, and postreplication repair–were sensitive to FA, indicating FA may cause various forms of DNA damage in yeast. The SKI complex and its associated factors, which regulate mRNA degradation by the exosome, were also required for FA tolerance, suggesting FA may have unappreciated effects on RNA stability. Furthermore, various strains involved in osmoregulation and stress response were sensitive to FA. Together, our results are generally consistent with FA-mediated damage to both DNA and RNA. Considering DNA repair and RNA degradation pathways are evolutionarily conserved from yeast to humans, mechanisms of FA toxicity identified in yeast may be relevant to human disease and genetic susceptibility.

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“…Specific cellular processes reported to promote cell survival include Nucleotide Excision Repair (NER) (20–22), proteasomal degradation (23), metalloproteases (24,25), the Fanconi Anemia pathway (26–29), and Homologous Recombination (HR) (20,22,30,31). We and others have also shown that formaldehyde can perturb the cell cycle and alter gene expression (21,30,32–35). However, based on prior literature, it was unclear to what extent the different DNA damage response and repair pathways protect cells from chronic formaldehyde exposures.…”

Section: Introductionmentioning

confidence: 86%

An RNAi screen in human cell lines reveals conserved DNA damage repair pathways that mitigate formaldehyde sensitivity

et al. 2018

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Formaldehyde is a ubiquitous DNA damaging agent, with human exposures occurring from both exogenous and endogenous sources. Formaldehyde exposure can result in multiple types of DNA damage, including DNA-protein crosslinks and thus, is representative of other exposures that induce DNA-protein crosslinks such as cigarette smoke, automobile exhaust, wood smoke, metals, ionizing radiation, and certain chemotherapeutics. Our objective in this study was to identify the genes necessary to mitigate formaldehyde toxicity following chronic exposure in human cells. We used siRNAs that targeted 320 genes representing all major human DNA repair and damage response pathways, in order to assess cell proliferation following siRNA depletion and subsequent formaldehyde treatment. Three unrelated human cell lines frequently used in genotoxicity studies (SW480, U-2 OS and GM00639) were used to identify common pathways involved in mitigating formaldehyde sensitivity. Although there were gene-specific differences among the cell lines, four inter-related cellular pathways were determined to mitigate formaldehyde toxicity: homologous recombination, DNA double-strand break repair, ionizing radiation response and DNA replication. Additional insight into cell line-specific response patterns was obtained by using a combination of exome sequencing and Cancer Cell Line Encyclopedia genomic data. The results of this DNA damage repair pathway-focused siRNA screen for formaldehyde toxicity in human cells provide a foundation for detailed mechanistic analyses of pathway-specific involvement in the response to environmentally-induced DNA-protein crosslinks and, more broadly, genotoxicity studies using human and other mammalian cell lines.

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Genetic effects of formaldehyde in yeast. I. Influence of the growth stages on killing and recombination

Cited by 30 publications

References 17 publications

Identification of Small Aliphatic Aldehydes in Pretreated Lignocellulosic Feedstocks and Evaluation of Their Inhibitory Effects on Yeast

Identification of Small Aliphatic Aldehydes in Pretreated Lignocellulosic Feedstocks and Evaluation of Their Inhibitory Effects on Yeast

Functional Toxicogenomic Profiling Expands Insight into Modulators of Formaldehyde Toxicity in Yeast

An RNAi screen in human cell lines reveals conserved DNA damage repair pathways that mitigate formaldehyde sensitivity

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