Genome-wide screen of genes required for caffeine tolerance in fission yeast.
Genome-wide screen of genes required for caffeine tolerance in fission yeast.
复制标题
DOI：
10.1371/journal.pone.0006619
复制
发表时间：
2009-08-12
期刊：
影响因子：
3.7
通讯作者：
Hidalgo E
中科院分区：
文献类型：
--
作者：
Calvo IA;Gabrielli N;Iglesias-Baena I;García-Santamarina S;Hoe KL;Kim DU;Sansó M;Zuin A;Pérez P;Ayté J;Hidalgo E
过量的咖啡因对所有真核细胞类型都有细胞毒性。我们的目标是研究细胞如何耐受这种药物的毒性剂量，以及咖啡因和氧化应激途径之间的关系。我们寻找粟酒裂殖酵母突变体，其在含咖啡因的平板上生长受到抑制。我们筛选了2,700个单倍体突变细胞，其中98个对咖啡因敏感。这些敏感克隆中突变的基因参与了许多细胞的作用，包括H2O2诱导的Pap1和Sty1应激途径，完整性和钙调神经磷酸酶途径，细胞形态和染色质重塑。我们已经研究了氧化应激途径在感知和促进咖啡因生存中的作用。Pap1和Sty1通路都是对咖啡因的正常耐受所必需的，但只有Sty1通路被药物激活。缺乏Pap1的细胞由于外排泵Hba2的表达减少而对咖啡因敏感。是吗？Hba2细胞对咖啡因敏感，Pap1通路的组成性激活以Hba2依赖性方式增强对咖啡因的抵抗力。通过我们对咖啡因敏感的全基因组筛选，粟酒裂殖酵母缺失收集，我们已经证明了一些氧化应激途径组分对野生型药物耐受性的重要性。
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. 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 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 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. 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.
登录
查看更多内容
影响因子：
4.8
作者：
Barba, Gregorio;Soto, Teresa;Cansado, Jose
通讯作者：
Cansado, Jose
影响因子：
3.1
作者：
Benko, Z;Fenyvesvolgyi, C;Sipiczki, M
通讯作者：
Sipiczki, M
影响因子：
5.3
作者：
COSTIGAN, C;GEHRUNG, S;SNYDER, M
通讯作者：
SNYDER, M
影响因子：
2.6
作者：
Hentges, P;Van Driessche, B;Carr, AM
通讯作者：
Carr, AM
影响因子：
4.8
作者：
Castillo, EA;Vivancos, AP;Hidalgo, E
通讯作者：
Hidalgo, E