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 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.
Hamimes
Samia
S
International Agency for Research on Cancer, 150 Cours Albert Thomas, 69372 Lyon, France.
Arakawa
Hiroshi
H
Stasiak
Alicja Z
AZ
Kierzek
Andrzej M
AM
Hirano
Seiki
S
Yang
Yun-Gui
YG
Takata
Minoru
M
Stasiak
Andrzej
A
Buerstedde
Jean-Marie
JM
Van Dyck
Eric
E
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D002645:Chickens; D002945:Cisplatin / Q000494:pharmacology*; D003001:Cloning, Molecular; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020224:Expressed Sequence Tags; D006801:Humans; D007700:Kinetics; D008390:Markov Chains; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011995:Recombination, Genetic; D016415:Sequence Alignment; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D014714:Vertebrates
D004268:DNA-Binding Proteins; C499652:RDM1 protein, human; D002945:Cisplatin