Gamma-rays-induced death of human cells carrying mutations of BRCA1 or BRCA2

被引:135
作者
Foray, N
Randrianarison, V
Marot, D
Perricaudet, M
Lenoir, G
Feunteun, J
机构
[1] Inst Gustave Roussy, CNRS UMR 1599, Lab Genet Oncol, F-94805 Villejuif, France
[2] Inst Gustave Roussy, CNRS UMR 1582, Lab Vectorol & Transfert Genes, F-94805 Villejuif, France
[3] Univ Lyon 1, CNRS UMR 5641, Lab Genet & Canc, F-69365 Lyon, France
关键词
BRCA1; BRCA2; DNA repair; radiation;
D O I
10.1038/sj.onc.1203165
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:7334 / 7342
页数:9
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