BRCA1, BRCA2, and Rad51 operate in a common DNA damage response pathway.
The two major hereditary breast cancer susceptibility genes, BRCA1 and BRCA2, are associated with early-onset breast and/or ovarian cancer and encode products that each interact with the product of the eukaryotic RecA homologue, hRad51. We have recently found that BRCA1 and BRCA2 coexist in a common biochemical complex. The two proteins also colocalize in subnuclear foci in somatic cells as well as on the axial elements of developing synaptonemal complexes in meiotic cells. Thus, BRCA1 and BRCA2 participate in a common DNA damage response pathway associated with the activation of homologous recombination and double-strand break repair. Dysfunction of this pathway may be a general phenomenon in the majority of cases of hereditary breast and/or ovarian cancer. The BRCA1/BRCA2 complex may function in postreplicational repair processes activated during the DNA synthesis stage of the cell cycle.
Chen
J J
JJ
The Dana-Faber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA.
Silver
D
D
Cantor
S
S
Livingston
D M
DM
Scully
R
R
D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000235:genetics*; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D019398:Genes, BRCA1; D020022:Genetic Predisposition to Disease; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics*; D051135:Rad51 Recombinase; D011995:Recombination, Genetic; D014157:Transcription Factors / Q000235:genetics*
D024682:BRCA2 Protein; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D014157:Transcription Factors; C495153:RAD51 protein, human; D051135:Rad51 Recombinase