Stable Interaction Between the Products of the BRCA1 and BRCA2 Tumor Suppressor Genes in Mitotic and Meiotic Cells

Mol Cell. 1998 Sep;2(3):317-28. doi: 10.1016/s1097-2765(00)80276-2.

Abstract

BRCA1 and BRCA2 account for most cases of familial, early onset breast and/or ovarian cancer and encode products that each interact with hRAD51. Results presented here show that BRCA1 and BRCA2 coexist in a biochemical complex and colocalize in subnuclear foci in somatic cells and on the axial elements of developing synaptonemal complexes. Like BRCA1 and RAD51, BRCA2 relocates to PCNA+ replication sites following exposure of S phase cells to hydroxyurea or UV irradiation. Thus, BRCA1 and BRCA2 participate, together, in a pathway(s) associated with the activation of double-strand break repair and/or homologous recombination. Dysfunction of this pathway may be a general phenomenon in the majority of cases of hereditary breast and/or ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies, Monoclonal
  • BRCA1 Protein / analysis
  • BRCA1 Protein / metabolism*
  • BRCA2 Protein
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Cell Line
  • Cell Nucleus / ultrastructure
  • Chromosome Mapping
  • DNA Damage
  • DNA Repair
  • DNA Replication
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / genetics
  • Female
  • Genes, BRCA1*
  • Genes, Tumor Suppressor*
  • Humans
  • Meiosis
  • Mitosis
  • Neoplasm Proteins / analysis
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism*
  • Ovarian Neoplasms / genetics
  • Rad51 Recombinase
  • Transcription Factors / analysis
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*
  • Transfection
  • Tumor Cells, Cultured
  • Zygote / cytology

Substances

  • Antibodies, Monoclonal
  • BRCA1 Protein
  • BRCA2 Protein
  • DNA-Binding Proteins
  • Neoplasm Proteins
  • Transcription Factors
  • RAD51 protein, human
  • Rad51 Recombinase