Gamma-rays-induced death of human cells carrying mutations of BRCA1 or BRCA2.
There is now evidence to suggest that BRCA1 and BRCA2 are involved in the response of cells to DNA damage and cell cycle checkpoint control. This report examines the death pathways of human cells with various BRCA1 and BRCA2 genotypes after exposure to gamma-rays. A lack of functional BRCA1 and BRCA2 led to defective repair of DNA double-strand breaks in irradiated cells. This impairment resulted in a relaxation of cell cycle checkpoints, production of micronuclei, and a loss of proliferative capacity. Heterozygous BRCA1 and BRCA2 mutations also led to enhanced radiosensitivity, with an impaired proliferative capacity after irradiation. The existence of a phenotype related to radiosensitivity in BRCA1+/- and BRCA2+/- cells raises the question of the response of heterozygous women to radiation.
Foray
N
N
Laboratoire de Génétique Oncologique, CNRS UMR #1599, Institut Gustave-Roussy, 94805 Villejuif Cedex, France.
Randrianarison
V
V
Marot
D
D
Perricaudet
M
M
Lenoir
G
G
Feunteun
J
J
D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy; D016923:Cell Death / Q000235:genetics* / Q000528:radiation effects; D004249:DNA Damage / Q000528:radiation effects; D004260:DNA Repair / Q000528:radiation effects; D005260:Female; D006801:Humans; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured
D019313:BRCA1 Protein; D024682:BRCA2 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors