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J. Biol. Chem., Vol. 280, Issue 10, 9225-9235, March 11, 2005

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RDM1, a Novel RNA Recognition Motif (RRM)-containing Protein Involved in the Cell Response to Cisplatin in Vertebrates^*

Samia Hamimes, Hiroshi Arakawa¶, Alicja Z. Stasiak||, Andrzej M. Kierzek**, Seiki Hirano, Yun-Gui Yang, Minoru Takata, Andrzej Stasiak||, Jean-Marie Buerstedde¶, and Eric Van Dyck¶¶

From the International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon, France, ^¶Institute for Molecular Radiobiology, GSF, Ingolstaedter Landstrasse 1, D-85764 Neuherberg-Munich, Germany, ^||Laboratoire d'Analyse Ultrastructurale, Université de Lausanne, 1015 Lausanne, Switzerland, ^**SBMS, University of Surrey, Guildford GU2 7XH, United Kingdom, Immunology and Molecular Genetics, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan, and Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5A, 02-106 Warsaw, Poland

A variety of cellular proteins has the ability to recognize DNA lesions induced by the anti-cancer drug cisplatin, with diverse consequences on their repair and on the therapeutic effectiveness of this drug. We report a novel gene involved in the cell response to cisplatin in vertebrates. The RDM1 gene (for RAD52 Motif 1) was identified while searching databases for sequences showing similarities to RAD52, a protein involved in homologous recombination and DNA double-strand break repair. Ablation of RDM1 in the chicken B cell line DT40 led to a more than 3-fold increase in sensitivity to cisplatin. However, RDM1^–/– cells were not hypersensitive to DNA damages caused by ionizing radiation, UV irradiation, or the alkylating agent methylmethane sulfonate. The RDM1 protein displays a nucleic acid binding domain of the RNA recognition motif (RRM) type. By using gel-shift assays and electron microscopy, we show that purified, recombinant chicken RDM1 protein interacts with single-stranded DNA as well as double-stranded DNA, on which it assembles filament-like structures. Notably, RDM1 recognizes DNA distortions induced by cisplatin-DNA adducts in vitro. Finally, human RDM1 transcripts are abundant in the testis, suggesting a possible role during spermatogenesis.

Received for publication, November 15, 2004 , and in revised form, December 10, 2004.

^* This work was supported in part by grants from La Ligue Contre le Cancer, Comité du Rhône, l'Association pour la Recherche sur le Cancer, Grant BU 631/2–1 from the Deutsche Forschungsgemeinshaft, by the European Union Framework V Programs "Chicken Image" and "Genetics in a Cell Line," and by Grant 3100-058841 from the Swiss National Science Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the DDBJ/GenBank^TM/EBI Data Bank with accession number(s) AB080727 and AB080728.

Both authors contributed equally to this work.

^¶¶ To whom correspondence should be addressed: Molecular Carcinogenesis, International Agency for Research on Cancer (IARC) 150 Cours Albert Thomas, 69732 Lyon, France. Tel.: 33-4-72-73-83-93; Fax: 33-4-72-73-83-23; E-mail: Vandyck{at}iarc.fr.

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