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SYSTEMS BIOLOGY, MOLECULAR BIOLOGY, AND GENE REGULATION

Ribonucleotide Reductase Regulation in Response to Genotoxic Stress in Arabidopsis^1,[W]

Institut de Biologie Moléculaire des Plantes du Centre National de la Recherche Scientifique, Université de Strasbourg, 67084 Strasbourg cedex, France (H.R., J.L., M.K., S.H., V.C., G.H., M.-E.C.); Department of Molecular, Cellular, and Biomedical Sciences, University of New Hampshire, Durham, New Hampshire 03824 (K.M.C.); and CEA, IBEB, SBVME, Centre National de la Recherche Scientifique-UMR6191, Université de La Méditerranée, Laboratoire de Génétique et Biophysique des plantes, 13288 Marseille cedex 9, France (M.-H.M.)

Ribonucleotide reductase (RNR) is an essential enzyme that provides dNTPs for DNA replication and repair. Arabidopsis (Arabidopsis thaliana) encodes three AtRNR2-like catalytic subunit genes (AtTSO2, AtRNR2A, and AtRNR2B). However, it is currently unclear what role, if any, each gene contributes to the DNA damage response, and in particular how each gene is transcriptionally regulated in response to replication blocks and DNA damage. To address this, we investigated transcriptional changes of 17-d-old Arabidopsis plants (which are enriched in S-phase cells over younger seedlings) in response to the replication-blocking agent hydroxyurea (HU) and to the DNA double-strand break inducer bleomycin (BLM). Here we show that AtRNR2A and AtRNR2B are specifically induced by HU but not by BLM. Early AtRNR2A induction is decreased in an atr mutant, and this induction is likely required for the replicative stress checkpoint since rnr2a mutants are hypersensitive to HU, whereas AtRNR2B induction is abolished in the rad9-rad17 double mutant. In contrast, AtTSO2 transcription is only activated in response to double-strand breaks (BLM), and this activation is dependent upon AtE2Fa. Both TSO2 and E2Fa are likely required for the DNA damage response since tso2 and e2fa mutants are hypersensitive to BLM. Interestingly, TSO2 gene expression is increased in atr versus wild type, possibly due to higher ATM expression in atr. On the other hand, a transient ATR-dependent H4 up-regulation was observed in wild type in response to HU and BLM, perhaps linked to a transient S-phase arrest. Our results therefore suggest that individual RNR2-like catalytic subunit genes participate in unique aspects of the cellular response to DNA damage in Arabidopsis.

The author responsible for distribution of materials integral to the findings presented in this article in accordance with the policy described in the Instructions for Authors (www.plantphysiol.org) is: Marie-Edith Chabouté (marie-edith.chaboute{at}ibmp-ulp.u-strasbg.fr).

^[W] The online version of this article contains Web-only data.

www.plantphysiol.org/cgi/doi/10.1104/pp.109.140053

^* Corresponding author; e-mail marie-edith.chaboute{at}ibmp-ulp.u-strasbg.fr.

Received April 17, 2009; accepted June 28, 2009; published July 1, 2009.