Attenuation of the formation of DNA-repair foci containing RAD51 in Fanconi anaemia

Carcinogenesis. 2002 Jul;23(7):1121-6. doi: 10.1093/carcin/23.7.1121.


The role of the Fanconi anaemia genes in DNA repair was examined by a quantitative analysis of nuclear DNA repair foci in FA primary fibroblasts after ionising irradiation using antibodies directed against RAD51, MRE11 and BRCA1 for visualisation. IR induced foci detected with anti-RAD51, but not those detected with anti-MRE11, are reduced in fibroblasts of all eight FA complementation groups in comparison to control cells. Correction of FA-A, FA-C and FA-G cells by retroviral cDNA transfer specifically corrected the RAD51-foci response but did not affect formation of foci containing BRCA1 or MRE11. Since all FA cells, except FA-D1, lack the monoubiquitinated FANCD2-L protein, this isoform is likely to be involved in the formation of nuclear foci containing RAD51 in diploid FA cells. FA-D1 cells show the same attenuation in RAD51 foci formation, suggesting that the unknown FANCD1 protein is similarly involved in RAD51 foci formation, either independently or as a subsequent step in the FANCD2 pathway. These findings indicate that Fanconi anaemia cells have an impairment in the RAD51-dependent homologous recombination pathway for DNA repair, explaining their chromosomal instability and extreme sensitivity to DNA cross-linking agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • BRCA1 Protein / genetics
  • BRCA1 Protein / metabolism
  • Blotting, Western
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Cells, Cultured / radiation effects
  • DNA Repair / genetics*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Fanconi Anemia / genetics*
  • Fanconi Anemia / metabolism*
  • Fibroblasts / radiation effects
  • Fluorescent Antibody Technique
  • Green Fluorescent Proteins
  • Humans
  • Luminescent Proteins / metabolism
  • MRE11 Homologue Protein
  • Rad51 Recombinase
  • Retroviridae
  • Transfection
  • X-Rays


  • BRCA1 Protein
  • DNA-Binding Proteins
  • Luminescent Proteins
  • MRE11 protein, human
  • Green Fluorescent Proteins
  • RAD51 protein, human
  • Rad51 Recombinase
  • MRE11 Homologue Protein