Molecular Genetics and Genomics

, Volume 275, Issue 2, pp 114–124 | Cite as

Role of the iron mobilization and oxidative stress regulons in the genomic response of yeast to hydroxyurea

  • Caroline Dubacq
  • Anne Chevalier
  • Régis Courbeyrette
  • Cyrille Petat
  • Xavier Gidrol
  • Carl Mann
Original Paper

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 yap1Δ 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 aft1Δ aft2Δ 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.

Keywords

DNA damage response Hydroxyurea Aft1 and Yap1 transcription factors Ribonucleotide reductase Yeast 

Abbreviations

HU

Hydroxyurea

RNR

Ribonucleotide reductase

DDR

DNA Damage Response

ESR

Environmental stress response

RT-PCR

Reverse transcriptase polymerase chain reaction

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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Caroline Dubacq
    • 1
    • 4
  • Anne Chevalier
    • 1
  • Régis Courbeyrette
    • 1
  • Cyrille Petat
    • 2
  • Xavier Gidrol
    • 2
  • Carl Mann
    • 1
    • 3
  1. 1.Service de Biochimie et de Génétique Moléculaire, Gif-sur-YvetteFrance
  2. 2.Service de Génomique Fonctionnelle du CEAEvry CedexFrance
  3. 3.Department of Biochemistry and Molecular Biology, F. Edward Hébert School of MedicineUSUHSBethesdaUSA
  4. 4.Ecole Normale SupérieureParisFrance

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