Saleh-Gohari Nasrollah, Helleday Thomas
The Institute for Cancer Studies, University of Sheffield, Medical School, Beech Hill Road, Sheffield S10 2RX, UK.
Oncogene. 2004 Dec 2;23(56):9136-41. doi: 10.1038/sj.onc.1208178.
The BRCA2 tumour suppressor protein is involved in maintaining genetic stability through its role in homologous recombination (HR), where it mediates RAD51-dependent strand invasion. Here, we show that BRCA2-defective cells are not completely impaired in HR by strand invasion although the spontaneous HR rate is 10-fold lower than that in wild-type cells. Furthermore, a DNA double-strand break (DSB) triggers HR repair by strand invasion also in BRCA2-defective cells, but less efficiently. Thus, either the strand invasion pathway(s) in which BRCA2 operates is still operative in the absence of a functional BRCA2, albeit at a reduced frequency, or there is a separate pathway for strand invasion still functional in BRCA2-deficient cells. Consistent with the latter hypothesis, we show that HR events occurring in BRCA2-defective cells differ from HR events in wild-type cells. These data suggest that BRCA2-defective hamster cells are impaired in short tract gene conversion but maintain proficiency in sister chromatid exchange.
BRCA2肿瘤抑制蛋白通过其在同源重组（HR）中的作用参与维持遗传稳定性，在同源重组中它介导RAD51依赖的链侵入。在此，我们表明，尽管自发HR率比野生型细胞低10倍，但BRCA2缺陷型细胞在通过链侵入进行的HR中并未完全受损。此外，DNA双链断裂（DSB）在BRCA2缺陷型细胞中也会通过链侵入触发HR修复，但效率较低。因此，要么BRCA2发挥作用的链侵入途径在缺乏功能性BRCA2时仍可发挥作用，尽管频率降低，要么存在一条独立的链侵入途径在BRCA2缺陷型细胞中仍发挥功能。与后一种假设一致，我们表明BRCA2缺陷型细胞中发生的HR事件与野生型细胞中的HR事件不同。这些数据表明，BRCA2缺陷型仓鼠细胞在短片段基因转换中受损，但在姐妹染色单体交换方面保持能力。
