STABLE INTERACTION BETWEEN THE PRODUCTS OF THE BRCA1 AND BRCA2 TUMOR-SUPPRESSOR GENES IN MITOTIC AND MEIOTIC CELLS

BRCA1 and BRCA2 account for most cases of familial, early onset breast and/or ovarian cancer and encode products that each interact with hRA D51. Results presented here show that BRCA1 and BRCA2 coexist in a bio chemical complex and colocalize in subnuclear foci in somatic cells an d on the axial elements of developing synaptonemal complexes. Like BRC A1 and RAD51, BRCA2 relocates to PCNA(+) replication sites following e xposure 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 recombinati on. Dysfunction of this pathway may be a general phenomenon in the maj ority of cases of hereditary breast and/or ovarian cancer.