Sodium selenide toxicity is mediated by O2-dependent DNA breaks.

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 sod...

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Autores principales:	Gérald Peyroche, Cosmin Saveanu, Marc Dauplais, Myriam Lazard, François Beuneu, Laurence Decourty, Christophe Malabat, Alain Jacquier, Sylvain Blanquet, Pierre Plateau
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e9c6b80a22464d87a2bdee148b2d7bd3
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spelling	oai:doaj.org-article:e9c6b80a22464d87a2bdee148b2d7bd32021-11-18T07:19:29ZSodium selenide toxicity is mediated by O2-dependent DNA breaks.1932-620310.1371/journal.pone.0036343https://doaj.org/article/e9c6b80a22464d87a2bdee148b2d7bd32012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22586468/?tool=EBIhttps://doaj.org/toc/1932-6203Hydrogen 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.Gérald PeyrocheCosmin SaveanuMarc DauplaisMyriam LazardFrançois BeuneuLaurence DecourtyChristophe MalabatAlain JacquierSylvain BlanquetPierre PlateauPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 5, p e36343 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Gérald Peyroche Cosmin Saveanu Marc Dauplais Myriam Lazard François Beuneu Laurence Decourty Christophe Malabat Alain Jacquier Sylvain Blanquet Pierre Plateau Sodium selenide toxicity is mediated by O2-dependent DNA breaks.
description	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.
format	article
author	Gérald Peyroche Cosmin Saveanu Marc Dauplais Myriam Lazard François Beuneu Laurence Decourty Christophe Malabat Alain Jacquier Sylvain Blanquet Pierre Plateau
author_facet	Gérald Peyroche Cosmin Saveanu Marc Dauplais Myriam Lazard François Beuneu Laurence Decourty Christophe Malabat Alain Jacquier Sylvain Blanquet Pierre Plateau
author_sort	Gérald Peyroche
title	Sodium selenide toxicity is mediated by O2-dependent DNA breaks.
title_short	Sodium selenide toxicity is mediated by O2-dependent DNA breaks.
title_full	Sodium selenide toxicity is mediated by O2-dependent DNA breaks.
title_fullStr	Sodium selenide toxicity is mediated by O2-dependent DNA breaks.
title_full_unstemmed	Sodium selenide toxicity is mediated by O2-dependent DNA breaks.
title_sort	sodium selenide toxicity is mediated by o2-dependent dna breaks.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/e9c6b80a22464d87a2bdee148b2d7bd3
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Sodium selenide toxicity is mediated by O2-dependent DNA breaks.

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