RDM1, a novel RNA recognition motif (RRM)-containing protein involved in the cell response to cisplatin in vertebrates

J Biol Chem. 2005 Mar 11;280(10):9225-35. doi: 10.1074/jbc.M412874200. Epub 2004 Dec 14.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

  • DNA-Binding Proteins
  • RDM1 protein, human
  • Cisplatin

Associated data

  • GENBANK/AB080727
  • GENBANK/AB080728