Roles of BRCA1 and BRCA2 in homologous recombination, DNA replication fidelity and the cellular response to ionizing radiation
Roles of BRCA1 and BRCA2 in homologous recombination, DNA replication fidelity and the cellular response to ionizing radiation
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DOI：
10.1038/sj.onc.1206678
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发表时间：
2003-09-01
期刊：
影响因子：
8
通讯作者：
Kachnic, LA
中科院分区：
文献类型：
--
作者：
Powell, SN;Kachnic, LA
遗传两种乳腺癌易感基因BRCA1和BRCA2中的任何一种有缺陷的拷贝都会使个体易患乳腺癌和卵巢癌。目前在确定这些基因功能方面的进展表明，它们参与了一个共同的途径，以促进有序的同源重组，从而保持基因组的完整性。由于同源重组中的这种缺陷，BRCA携带者产生的肿瘤可能对电离辐射更敏感。本文综述了最近关于DNA修复缺陷性质的研究，并强调了关于BRCA基因肿瘤抑制悖论的未解决问题。尚未解决的谜团是，将缺乏brca的细胞从不能存活的细胞转变为能够无限生长的肿瘤细胞必须发生的其他遗传变化。
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.