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dc.contributor.authorThornton, Gemma
dc.contributor.authorWilkinson, Caroline R M
dc.contributor.authorToone, W Mark
dc.contributor.authorJones, Nic
dc.date.accessioned2009-07-21T16:58:05Z
dc.date.available2009-07-21T16:58:05Z
dc.date.issued2005-10
dc.identifier.citationA novel pathway determining multidrug sensitivity in Schizosaccharomyces pombe. 2005, 10 (10):941-51 Genes Cellsen
dc.identifier.issn1356-9597
dc.identifier.pmid16164595
dc.identifier.doi10.1111/j.1365-2443.2005.00891.x
dc.identifier.urihttp://hdl.handle.net/10541/74836
dc.description.abstractIn this study, we show that a mutation isolated during a screen for determinants of chemosensitivity in S. pombe results in loss of function of a previously uncharacterized protein kinase now named Hal4. Hal4 shares sequence homology to Hal4 and Hal5 in S. cerevisiae, and previous evidence indicates that these kinases positively regulate the major potassium transporter Trk1,2 and thereby maintain the plasma membrane potential. Disruption of this ion homeostasis pathway results in a hyperpolarized membrane and a concomitant increased sensitivity to cations. We demonstrate that a mutation in hal4+ results in hyperpolarization of the plasma membrane. In addition to the original selection agent, the hal4-1 mutant is sensitive to a variety of chemotherapeutic agents and stress-inducing compounds. Furthermore, this wider chemosensitive phenotype is also displayed by corresponding mutants in S. cerevisiae, and in a trk1deltatrk2delta double deletion mutant in S. pombe. We propose that this pathway and its role in regulating the plasma membrane potential may act as a pleiotropic determinant of sensitivity to chemotherapeutic agents.
dc.language.isoenen
dc.subject.meshCation Transport Proteins
dc.subject.meshCations
dc.subject.meshCell Membrane
dc.subject.meshDose-Response Relationship, Drug
dc.subject.meshDrug Resistance, Multiple, Fungal
dc.subject.meshEscherichia coli
dc.subject.meshGene Expression Regulation, Fungal
dc.subject.meshGenes, Fungal
dc.subject.meshMembrane Potentials
dc.subject.meshMutation
dc.subject.meshPotassium Chloride
dc.subject.meshProtein Kinases
dc.subject.meshSaccharomyces cerevisiae Proteins
dc.subject.meshSchizosaccharomyces
dc.subject.meshSchizosaccharomyces pombe Proteins
dc.subject.meshSequence Homology
dc.titleA novel pathway determining multidrug sensitivity in Schizosaccharomyces pombe.en
dc.typeArticleen
dc.contributor.departmentPaterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester, M20 4BX, UK.en
dc.identifier.journalGenes to Cellsen
html.description.abstractIn this study, we show that a mutation isolated during a screen for determinants of chemosensitivity in S. pombe results in loss of function of a previously uncharacterized protein kinase now named Hal4. Hal4 shares sequence homology to Hal4 and Hal5 in S. cerevisiae, and previous evidence indicates that these kinases positively regulate the major potassium transporter Trk1,2 and thereby maintain the plasma membrane potential. Disruption of this ion homeostasis pathway results in a hyperpolarized membrane and a concomitant increased sensitivity to cations. We demonstrate that a mutation in hal4+ results in hyperpolarization of the plasma membrane. In addition to the original selection agent, the hal4-1 mutant is sensitive to a variety of chemotherapeutic agents and stress-inducing compounds. Furthermore, this wider chemosensitive phenotype is also displayed by corresponding mutants in S. cerevisiae, and in a trk1deltatrk2delta double deletion mutant in S. pombe. We propose that this pathway and its role in regulating the plasma membrane potential may act as a pleiotropic determinant of sensitivity to chemotherapeutic agents.


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