Nbs1 is essential for DNA repair by homologous recombination in higher vertebrate cells
Nbs1 is essential for DNA repair by homologous recombination in higher vertebrate cells
复制标题
DOI：
10.1038/nature01125
复制
发表时间：
2002-11-07
期刊：
影响因子：
64.8
通讯作者：
Komatsu, K
中科院分区：
文献类型：
--
作者：
Tauchi, H;Kobayashi, J;Komatsu, K
双链断裂发生在DNA复制过程中，也可由电离辐射引起。至少有两种途径可以修复这种断裂：非同源末端连接和同源重组（HR）。虽然这些途径在本质上是相互独立的，但在酿酒酵母中，蛋白Mre11、Rad50和Xrs2可能参与了这两种途径(1)。在脊椎动物细胞中，我们对Mre11-Rad50-Nbs1复合物在修复双链断裂中的确切功能知之甚少，因为mre11 -和rad50 -null突变是致命的(2)。在这里，我们发现Nbs1对高等脊椎动物细胞中hr介导的修复至关重要。Nbs1的破坏减少了基因转换和姐妹染色单体交换，类似于其他hr缺陷突变体(3)。事实上，位点特异性双链断裂修复试验显示，在nbs1断裂的细胞中，发生这种断裂后，HR事件显著减少。在Nbs1破坏的细胞中观察到的罕见重组体经常被发现具有异常的结构，这可能是由不寻常的交叉事件引起的，这表明Nbs1复合体可能需要处理重组中间体。
Double-strand breaks occur during DNA replication and are also induced by ionizing radiation. There are at least two pathways which can repair such breaks: non-homologous end joining and homologous recombination (HR). Although these pathways are essentially independent of one another, it is possible that the proteins Mre11, Rad50 and Xrs2 are involved in both pathways in Saccharomyces cerevisiae(1). In vertebrate cells, little is known about the exact function of the Mre11-Rad50-Nbs1 complex in the repair of double-strand breaks because Mre11-andRad50-null mutations are lethal(2). Here we show that Nbs1 is essential for HR-mediated repair in higher vertebrate cells. The disruption of Nbs1 reduces gene conversion and sister chromatid exchanges, similar to other HR-deficient mutants(3). In fact, a site-specific double-strand break repair assay showed a notable reduction of HR events following generation of such breaks in Nbs1-disrupted cells. The rare recombinants observed in the Nbs1-disrupted cells were frequently found to have aberrant structures, which possibly arise from unusual crossover events, suggesting that the Nbs1 complex might be required to process recombination intermediates.