Roles of BRCA1 and BRCA2 in homologous recombination, DNA replication fidelity and the cellular response to ionizing radiation

被引:275
作者
Powell, SN
Kachnic, LA
机构
[1] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA
[2] Boston Med Ctr, Dept Radiat Oncol, Boston, MA USA
关键词
breast cancer; BRCA genes; tumor suppressor genes; DNA repair; ionizing radiation; homologous recombination; DNA replication;
D O I
10.1038/sj.onc.1206678
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
Inheritance of one defective copy of either of the two breast cancer susceptibility genes, BRCA1 and BRCA2, predisposes individuals to breast and ovarian cancers. Current progress in determining the function of these genes suggests that they participate in a common pathway to facilitate orderly homologous recombination and thereby maintain genomic integrity. As a consequence of this defect in homologous recombination, tumors that arise in BRCA carriers are likely to be more sensitive to ionizing radiation. This review summarizes recent investigations about the nature of the defect in DNA repair, and highlights the unanswered questions about the tumor suppressor paradox of BRCA genes. The unsolved mystery is the other genetic changes that must occur to turn a BRCA-deficient cell from a nonviable cell into a tumor cell capable of endless growth.
引用
收藏
页码:5784 / 5791
页数:8
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