BRCA2-dependent and independent formation of RAD51 nuclear foci

Oncogene. 2003 Feb 27;22(8):1115-23. doi: 10.1038/sj.onc.1206263.


The formation of RAD51 foci in response to ionizing radiation (IR) represents an important step in the repair of DNA double-strand breaks. RAD51 foci also appear during S phase and are thought to be required for the restart of stalled or broken replication forks. The RAD51 recombinase interacts directly with the breast cancer-associated tumour suppressor BRCA2, an interaction that is required for normal recombination proficiency, radiation resistance and genome stability. In CAPAN-1 cells, which express a truncated form of BRCA2 that is cytoplasmic because of loss of the nuclear localization signal, the formation of IR-induced RAD51 foci is impaired. In this work, we show that S-phase RAD51 foci form normally in CAPAN-1 cells expressing truncated BRCA2. Moreover, we find that RAD51 specifically associates with chromatin at S phase in a reaction that is BRCA2-independent. The observed BRCA2-dependent and independent formation of RAD51 foci shows that intact BRCA2 is not required for RAD51 focus formation per se, leading us to suggest that S phase and IR-induced RAD51 foci assemble by distinct pathways with defined protein requirements.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • BRCA2 Protein / deficiency
  • BRCA2 Protein / metabolism*
  • Breast Neoplasms / pathology
  • Carcinoma / pathology
  • Cell Nucleus / metabolism
  • Chromatin / metabolism
  • Cytoplasm / metabolism
  • DNA Damage
  • DNA Repair / genetics
  • DNA Repair / physiology*
  • DNA Replication / genetics
  • DNA Replication / physiology*
  • DNA, Neoplasm / radiation effects
  • DNA-Binding Proteins / metabolism*
  • Genes, BRCA2
  • HeLa Cells / radiation effects
  • Humans
  • Multienzyme Complexes / metabolism*
  • Neoplasm Proteins / metabolism
  • Pancreatic Neoplasms / pathology
  • Protein Sorting Signals
  • Rad51 Recombinase
  • S Phase
  • Tumor Cells, Cultured / radiation effects


  • BRCA2 Protein
  • Chromatin
  • DNA, Neoplasm
  • DNA-Binding Proteins
  • Multienzyme Complexes
  • Neoplasm Proteins
  • Protein Sorting Signals
  • RAD51 protein, human
  • Rad51 Recombinase