Ionizing radiation-induced Rad51 nuclear focus formation is cell cycle-regulated and defective in both ATM(-/-) and c-Abl(-/-) cells

Mutat Res. 2003 Apr 9;525(1-2):85-92. doi: 10.1016/s0027-5107(03)00009-5.

Abstract

In eukaryotes, DNA double-strand breaks (DSBs) can be repaired by either non-homologous end-joining (NHEJ) or homologous recombination (HR) pathways. Rad50 protein is a component of the Rad50/NBS1/Mre11 nuclease complex that functions in both the NHEJ and recombinational repair of DNA DSBs. On the other hand, Rad51 protein, a homolog of bacterial RecA and a member of the Rad52 epistasis group, plays a crucial role exclusively in the recombinational repair pathway. We analyzed the effects of cell cycle progression and genetic background on the ionizing radiation (IR)-induced Rad51 and Rad50 repair focus formation. Herein, we demonstrated that IR-induced Rad51, but not Rad50, nuclear focus formation was cell cycle-dependent. Furthermore, IR-induced Rad51 focus formation was defective in AT and c-Abl(-/-) cells, but not wild type or NBS cells. A decreased and delayed formation of Rad51 foci-containing nuclei was observed in AT cells upon IR, whereas in c-Abl(-/-) cells a decreased but not delayed formation of Rad51 foci-containing nuclei was observed. In conclusion, effective and prompt IR-induced Rad51 focus formation is cell cycle-regulated and requires both ATM and c-Abl.

MeSH terms

  • Acid Anhydride Hydrolases
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle / physiology
  • Cell Cycle / radiation effects*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Cycle Proteins / radiation effects
  • Cell Line
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Cell Nucleus / radiation effects*
  • Chromosome Breakage
  • DNA Damage
  • DNA Repair / physiology
  • DNA Repair / radiation effects
  • DNA Repair Enzymes*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / radiation effects*
  • Gamma Rays / adverse effects
  • Humans
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Nuclear Proteins / radiation effects
  • Protein-Serine-Threonine Kinases / deficiency
  • Protein-Serine-Threonine Kinases / genetics*
  • Proto-Oncogene Proteins c-abl / deficiency
  • Proto-Oncogene Proteins c-abl / genetics*
  • Rad51 Recombinase
  • Tumor Suppressor Proteins

Substances

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • NBN protein, human
  • Nuclear Proteins
  • Tumor Suppressor Proteins
  • Proto-Oncogene Proteins c-abl
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein-Serine-Threonine Kinases
  • RAD51 protein, human
  • Rad51 Recombinase
  • Acid Anhydride Hydrolases
  • Rad50 protein, human
  • DNA Repair Enzymes