title: Role of the iron mobilization and oxidative stress regulons in the genomic response of yeast to hydroxyurea.
abstract: Hydroxyurea (HU) is a specific inhibitor of ribonucleotide reductase and thus impairs dNTP synthesis and DNA replication. The long-term transcriptional response of yeast cells to hydroxyurea was investigated using DNA microarrays containing all yeast coding sequences. We show that the redox-responsive Yap regulon and the iron-mobilization Aft regulon are activated in yeast cells treated with HU. Yap1 accumulates in the nucleus in response to HU, but HU activation of the Yap regulon was only partially dependent on Yap1 and yap1Delta mutants were not hypersensitive to HU. In contrast, deletion of the AFT1 and AFT2 transcription factor genes blocked the HU activation of a subset of the Aft regulon and the aft1Delta aft2Delta double mutant was hypersensitive to HU in an iron-suppressible manner. These results highlight the importance of the redox and iron mobilization regulons in the cellular response to HU.
authors.affiliation: Service de Biochimie et de Génétique Moléculaire, CEA/Saclay, Gif-sur-Yvette, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Dubacq
authors.forename: Anne
authors.initials: A
authors.lastname: Chevalier
authors.forename: Régis
authors.initials: R
authors.lastname: Courbeyrette
authors.forename: Cyrille
authors.initials: C
authors.lastname: Petat
authors.forename: Xavier
authors.initials: X
authors.lastname: Gidrol
authors.forename: Carl
authors.initials: C
authors.lastname: Mann
mesh_terms: D025141:Drug Resistance, Fungal / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020869:Gene Expression Profiling; D016681:Genome, Fungal / Q000187:drug effects; D006918:Hydroxyurea / Q000494:pharmacology; D007501:Iron / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D018085:Regulon; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D007501:Iron; D012264:Ribonucleotide Reductases; C071570:SNF1-related protein kinases; D017346:Protein Serine-Threonine Kinases; D006918:Hydroxyurea