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 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.
Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
J
J
Chen
D P
DP
Silver
D
D
Walpita
S B
SB
Cantor
A F
AF
Gazdar
G
G
Tomlinson
F J
FJ
Couch
B L
BL
Weber
T
T
Ashley
D M
DM
Livingston
R
R
Scully
D000911:Antibodies, Monoclonal; D019313:BRCA1 Protein / Q000032:analysis / Q000378:metabolism*; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D002460:Cell Line; D002467:Cell Nucleus / Q000648:ultrastructure; D002874:Chromosome Mapping; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics; D005260:Female; D019398:Genes, BRCA1; D016147:Genes, Tumor Suppressor; D006801:Humans; D008540:Meiosis; D008938:Mitosis; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics; D051135:Rad51 Recombinase; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D015053:Zygote / Q000166:cytology
D000911:Antibodies, Monoclonal; D019313:BRCA1 Protein; D024682:BRCA2 Protein; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D014157:Transcription Factors; C495153:RAD51 protein, human; D051135:Rad51 Recombinase