BRCA2 is required for homology-directed repair of chromosomal breaks
BRCA2 is required for homology-directed repair of chromosomal breaks
复制标题
DOI：
10.1016/s1097-2765(01)00174-5
复制
发表时间：
2001-02-01
期刊：
影响因子：
16
通讯作者：
Jasin, M
中科院分区：
文献类型：
--
作者：
Moynahan, ME;Pierce, AJ;Jasin, M
BRCA 2肿瘤抑制因子通过DNA修复功能参与维持染色体稳定性。在这份报告中，我们研究了人类和小鼠细胞系含有不同的BRCA 2突变的能力，修复染色体断裂的同源重组。使用I-Scel内切核酸酶在特定染色体位点引入双链断裂，我们发现BRCA 2突变细胞系是重组缺陷的，使得同源定向修复减少6至>100倍，这取决于细胞系。因此，BRCA 2是必要的有效同源定向修复，大概与Rad 51重组酶。我们认为BRCA 2缺陷导致的同源性定向修复受损会导致染色体不稳定，并可能通过DNA损伤的修复缺失或错误修复导致肿瘤发生。
The BRCA2 tumor suppressor has been implicated in the maintenance of chromosomal stability through a function in DNA repair. In this report, we examine human and mouse cell lines containing different BRCA2 mutations for their ability to repair chromosomal breaks by homologous recombination. Using the I-Scel endonuclease to introduce a double-strand break at a specific chromosomal locus, we find that BRCA2 mutant cell lines are recombination deficient, such that homology-directed repair is reduced 6- to >100-fold, depending on the cell line. Thus, BRCA2 is essential for efficient homology-directed repair, presumably in conjunction with the Rad51 recombinase. We propose that impaired homology-directed repair caused by BRCA2 deficiency leads to chromosomal instability and, possibly, tumorigenesis, through lack of repair or misrepair of DNA damage.