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Sodium selenide toxicity is mediated by O2-dependent DNA breaks
- Source :
- PLoS ONE, PLoS ONE, 2012, 7 (5), pp.e36343. ⟨10.1371/journal.pone.0036343⟩, PLoS ONE, Public Library of Science, 2012, 7 (5), pp.e36343. ⟨10.1371/journal.pone.0036343⟩, PLoS ONE, Vol 7, Iss 5, p e36343 (2012)
- Publication Year :
- 2012
- Publisher :
- HAL CCSD, 2012.
-
Abstract
- International audience; Hydrogen selenide is a recurrent metabolite of selenium compounds. However, few experiments studied the direct link between this toxic agent and cell death. To address this question, we first screened a systematic collection of Saccharomyces cerevisiae haploid knockout strains for sensitivity to sodium selenide, a donor for hydrogen selenide (H(2)Se/HSe(-/)Se(2-)). Among the genes whose deletion caused hypersensitivity, homologous recombination and DNA damage checkpoint genes were over-represented, suggesting that DNA double-strand breaks are a dominant cause of hydrogen selenide toxicity. Consistent with this hypothesis, treatment of S. cerevisiae cells with sodium selenide triggered G2/M checkpoint activation and induced in vivo chromosome fragmentation. In vitro, sodium selenide directly induced DNA phosphodiester-bond breaks via an O(2)-dependent reaction. The reaction was inhibited by mannitol, a hydroxyl radical quencher, but not by superoxide dismutase or catalase, strongly suggesting the involvement of hydroxyl radicals and ruling out participations of superoxide anions or hydrogen peroxide. The (*)OH signature could indeed be detected by electron spin resonance upon exposure of a solution of sodium selenide to O(2). Finally we showed that, in vivo, toxicity strictly depended on the presence of O(2). Therefore, by combining genome-wide and biochemical approaches, we demonstrated that, in yeast cells, hydrogen selenide induces toxic DNA breaks through an O(2)-dependent radical-based mechanism.
- Subjects :
- MESH: Cell Death
Anatomy and Physiology
Yeast and Fungal Models
Haploidy
Toxicology
MESH: G2 Phase Cell Cycle Checkpoints
Gene Knockout Techniques
chemistry.chemical_compound
0302 clinical medicine
Molecular Cell Biology
Mannitol
Anaerobiosis
Homologous Recombination
Selenium Compounds
Cellular Stress Responses
MESH: Gene Knockout Techniques
0303 health sciences
Multidisciplinary
Cell Death
biology
Sodium selenide
Genomics
MESH: Haploidy
MESH: Saccharomyces cerevisiae
Aerobiosis
Functional Genomics
G2 Phase Cell Cycle Checkpoints
Biochemistry
030220 oncology & carcinogenesis
MESH: Genome, Fungal
Medicine
MESH: Mannitol
Genome, Fungal
MESH: Oxygen
Research Article
Cell Physiology
DNA damage
MESH: Hypersensitivity
Science
Toxic Agents
chemistry.chemical_element
Saccharomyces cerevisiae
Mycology
Microbiology
Superoxide dismutase
MESH: Homologous Recombination
03 medical and health sciences
Model Organisms
Genome Analysis Tools
MESH: Aerobiosis
Hydrogen selenide
MESH: Anaerobiosis
Hypersensitivity
Genome-Wide Association Studies
MESH: Chromosome Aberrations
[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
DNA Breaks, Single-Stranded
Fragmentation (cell biology)
Biology
030304 developmental biology
Chromosome Aberrations
MESH: DNA Breaks, Single-Stranded
MESH: Selenium Compounds
G2-M DNA damage checkpoint
Yeast
Oxygen
chemistry
biology.protein
Hydroxyl radical
Selenium
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Database :
- OpenAIRE
- Journal :
- PLoS ONE, PLoS ONE, 2012, 7 (5), pp.e36343. ⟨10.1371/journal.pone.0036343⟩, PLoS ONE, Public Library of Science, 2012, 7 (5), pp.e36343. ⟨10.1371/journal.pone.0036343⟩, PLoS ONE, Vol 7, Iss 5, p e36343 (2012)
- Accession number :
- edsair.doi.dedup.....f87141483461e973601e640d9fd91c1c