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M412874200v1
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Papers In Press, published online ahead of print December 14, 2004
J. Biol. Chem, 10.1074/jbc.M412874200
Submitted on November 15, 2004
Revised on December 10, 2004
Accepted on December 14, 2004

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

Molecular Carcinogenesis, International Agency for Research on Cancer, Lyon 69008

Corresponding Author: Vandyck{at}iarc.fr

A variety of cellular proteins have the ability to recognize DNA lesions induced by the anti-cancer drug cisplatin, with diverse consequences on their repair and the therapeutic effectiveness of this drug. We report a novel gene involved in the cell response to cisplatin in vertebrates. The RDM1 (for RAD52 Motif 1) gene was identified whilst 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. 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.


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