Ku DNA end-binding protein modulates homologous repair of double-strand breaks in mammalian cells
Ku DNA end-binding protein modulates homologous repair of double-strand breaks in mammalian cells
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DOI：
10.1101/gad.946401
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发表时间：
2001-12-15
影响因子：
10.5
通讯作者：
Jasin, M
中科院分区：
文献类型：
--
作者：
Pierce, AJ;Hu, P;Jasin, M
哺乳动物细胞中的染色体双链断裂（DSB）通过同源定向修复（HDR）（使用同源序列作为修复模板）或非同源末端连接（NHEJ）（其通常涉及DSB位点处的序列改变）来修复。为了表征这两种途径的相互关系，我们分析了NHEJ组分缺乏的细胞中DSB的HDR。我们发现HDR频率在Ku 70（-/-）、XRCC 4（-/-）和DNA-PKcs（-/-）细胞中增强，其中在Ku 70（-/-）细胞中的增加特别显著。姐妹染色单体交换和基因靶向频率都不依赖于这些NHEJ蛋白。Ru调制的两端与一端的染色体断裂模型来解释这些结果。
Chromosomal double-strand breaks (DSBs) in mammalian cells are repaired by either homology-directed repair (HDR), using a homologous sequence as a repair template, or nonhomologous end-joining (NHEJ), which often involves sequence alterations at the DSB site. To characterize the interrelationship of these two pathways, we analyzed HDR of a DSB in cells deficient for NHEJ components. We find that the HDR frequency is enhanced in Ku70(-/-), XRCC4(-/-), and DNA-PKcs(-/-) cells, with the increase being particularly striking in Ku70(-/-) cells. Neither sister-chromatid exchange nor gene-targeting frequencies show a dependence on these NHEJ proteins. A Ru-modulated two-ended versus one-ended chromosome break model is presented to explain these results.