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.
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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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Acknowledgements
We thank P.-L. Blaiseau, A. Dancis, A. Delaunay, Y. Pereira, M. Toledano, and Y. Yamaguchi-Iwai for providing yeast strains, plasmids, and discussions. We are grateful to M. Werner for access to the microarray analysis platform and for general support. C.D. was supported by an Allocation Couplée de l’Ecole Normale Supérieure de Paris. This work was also supported by grants from the Association pour la Recherche sur le Cancer (ARC number 4470).
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Communicated by A. Aguilera
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Dubacq, C., Chevalier, A., Courbeyrette, R. et al. Role of the iron mobilization and oxidative stress regulons in the genomic response of yeast to hydroxyurea. Mol Genet Genomics 275, 114–124 (2006). https://doi.org/10.1007/s00438-005-0077-5
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DOI: https://doi.org/10.1007/s00438-005-0077-5