Genome-wide screen of genes required for caffeine tolerance in fission yeast.

<h4>Background</h4>An excess of caffeine is cytotoxic to all eukaryotic cell types. We aim to study how cells become tolerant to a toxic dose of this drug, and the relationship between caffeine and oxidative stress pathways.<h4>Methodology/principal findings</h4>We searched f...

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Autores principales: Isabel A Calvo, Natalia Gabrielli, Iván Iglesias-Baena, Sarela García-Santamarina, Kwang-Lae Hoe, Dong Uk Kim, Miriam Sansó, Alice Zuin, Pilar Pérez, José Ayté, Elena Hidalgo
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Publicado: Public Library of Science (PLoS) 2009
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Acceso en línea:https://doaj.org/article/471ade7ebfe54409a0bfa95fab07d3f7
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spelling oai:doaj.org-article:471ade7ebfe54409a0bfa95fab07d3f72021-11-25T06:21:03ZGenome-wide screen of genes required for caffeine tolerance in fission yeast.1932-620310.1371/journal.pone.0006619https://doaj.org/article/471ade7ebfe54409a0bfa95fab07d3f72009-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19672306/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>An excess of caffeine is cytotoxic to all eukaryotic cell types. We aim to study how cells become tolerant to a toxic dose of this drug, and the relationship between caffeine and oxidative stress pathways.<h4>Methodology/principal findings</h4>We searched for Schizosaccharomyces pombe mutants with inhibited growth on caffeine-containing plates. We screened a collection of 2,700 haploid mutant cells, of which 98 were sensitive to caffeine. The genes mutated in these sensitive clones were involved in a number of cellular roles including the H(2)O(2)-induced Pap1 and Sty1 stress pathways, the integrity and calcineurin pathways, cell morphology and chromatin remodeling. We have investigated the role of the oxidative stress pathways in sensing and promoting survival to caffeine. The Pap1 and the Sty1 pathways are both required for normal tolerance to caffeine, but only the Sty1 pathway is activated by the drug. Cells lacking Pap1 are sensitive to caffeine due to the decreased expression of the efflux pump Hba2. Indeed, ?hba2 cells are sensitive to caffeine, and constitutive activation of the Pap1 pathway enhances resistance to caffeine in an Hba2-dependent manner.<h4>Conclusions/significance</h4>With our caffeine-sensitive, genome-wide screen of an S. pombe deletion collection, we have demonstrated the importance of some oxidative stress pathway components on wild-type tolerance to the drug.Isabel A CalvoNatalia GabrielliIván Iglesias-BaenaSarela García-SantamarinaKwang-Lae HoeDong Uk KimMiriam SansóAlice ZuinPilar PérezJosé AytéElena HidalgoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 8, p e6619 (2009)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Isabel A Calvo
Natalia Gabrielli
Iván Iglesias-Baena
Sarela García-Santamarina
Kwang-Lae Hoe
Dong Uk Kim
Miriam Sansó
Alice Zuin
Pilar Pérez
José Ayté
Elena Hidalgo
Genome-wide screen of genes required for caffeine tolerance in fission yeast.
description <h4>Background</h4>An excess of caffeine is cytotoxic to all eukaryotic cell types. We aim to study how cells become tolerant to a toxic dose of this drug, and the relationship between caffeine and oxidative stress pathways.<h4>Methodology/principal findings</h4>We searched for Schizosaccharomyces pombe mutants with inhibited growth on caffeine-containing plates. We screened a collection of 2,700 haploid mutant cells, of which 98 were sensitive to caffeine. The genes mutated in these sensitive clones were involved in a number of cellular roles including the H(2)O(2)-induced Pap1 and Sty1 stress pathways, the integrity and calcineurin pathways, cell morphology and chromatin remodeling. We have investigated the role of the oxidative stress pathways in sensing and promoting survival to caffeine. The Pap1 and the Sty1 pathways are both required for normal tolerance to caffeine, but only the Sty1 pathway is activated by the drug. Cells lacking Pap1 are sensitive to caffeine due to the decreased expression of the efflux pump Hba2. Indeed, ?hba2 cells are sensitive to caffeine, and constitutive activation of the Pap1 pathway enhances resistance to caffeine in an Hba2-dependent manner.<h4>Conclusions/significance</h4>With our caffeine-sensitive, genome-wide screen of an S. pombe deletion collection, we have demonstrated the importance of some oxidative stress pathway components on wild-type tolerance to the drug.
format article
author Isabel A Calvo
Natalia Gabrielli
Iván Iglesias-Baena
Sarela García-Santamarina
Kwang-Lae Hoe
Dong Uk Kim
Miriam Sansó
Alice Zuin
Pilar Pérez
José Ayté
Elena Hidalgo
author_facet Isabel A Calvo
Natalia Gabrielli
Iván Iglesias-Baena
Sarela García-Santamarina
Kwang-Lae Hoe
Dong Uk Kim
Miriam Sansó
Alice Zuin
Pilar Pérez
José Ayté
Elena Hidalgo
author_sort Isabel A Calvo
title Genome-wide screen of genes required for caffeine tolerance in fission yeast.
title_short Genome-wide screen of genes required for caffeine tolerance in fission yeast.
title_full Genome-wide screen of genes required for caffeine tolerance in fission yeast.
title_fullStr Genome-wide screen of genes required for caffeine tolerance in fission yeast.
title_full_unstemmed Genome-wide screen of genes required for caffeine tolerance in fission yeast.
title_sort genome-wide screen of genes required for caffeine tolerance in fission yeast.
publisher Public Library of Science (PLoS)
publishDate 2009
url https://doaj.org/article/471ade7ebfe54409a0bfa95fab07d3f7
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