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

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 g...

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Bibliographic Details
Published in:The Journal of biological chemistry 2005-03, Vol.280 (10), p.9225-9235
Main Authors: Hamimes, Samia, Arakawa, Hiroshi, Stasiak, Alicja Z., Kierzek, Andrzej M., Hirano, Seiki, Yang, Yun-Gui, Takata, Minoru, Stasiak, Andrzej, Buerstedde, Jean-Marie, Van Dyck, Eric
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Cell Line
Cell Survival
Chickens
Cisplatin - pharmacology
Cloning, Molecular
DNA Repair
DNA-Binding Proteins - deficiency
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Expressed Sequence Tags
Humans
Kinetics
Markov Chains
Models, Molecular
Molecular Sequence Data
Protein Conformation
Recombination, Genetic
Sequence Alignment
Sequence Deletion
Sequence Homology, Amino Acid
Vertebrates
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Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M412874200