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Genome-wide screen of genes required for caffeine tolerance in fission yeast
Calvo, Isabel A.; Gabrielli, Natalia; Iglesias Baena, Iván; García Santamarina, Sarela; Hoe, Kwang-Lae; Kim, Dong Uk; Sansó Martínez, Miriam; Zuin, Alice; Pérez, Pilar; Ayté del Olmo, José; Hidalgo Hernando, Elena
Background: An excess of caffeine is cytotoxic to all eukaryotic cell types. We aim to study how cells become tolerant to atoxic dose of this drug, and the relationship between caffeine and oxidative stress pathways.Methodology/Principal Findings: We searched for Schizosaccharomyces pombe mutants with inhibited growth on caffeinecontainingplates. 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 H2O2-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 aresensitive 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. Conclusions/Significance: With our caffeine-sensitive, genome-wide screen of an S. pombe deletion collection, we havedemonstrated the importance of some oxidative stress pathway components on wild-type tolerance to the drug.
02-07-2013
Cafeïna
Cèl·lules eucariotes -- Aspectes genètics
© 2009 Calvo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
http://creativecommons.org/licenses/by/2.5/
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info:eu-repo/semantics/publishedVersion
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