Ku DNA 末端结合蛋白调节哺乳动物细胞中双链断裂的同源修复。
Ku DNA end-binding protein modulates homologous repair of double-strand breaks in mammalian cells.
作者信息
Pierce A J, Hu P, Han M, Ellis N, Jasin M
机构信息
Cell Biology Program, Memorial Sloan-Kettering Cancer Center, and Cornell University Graduate School of Medical Sciences, New York, New York 10021, USA.
出版信息
Genes Dev. 2001 Dec 15;15(24):3237-42. doi: 10.1101/gad.946401.
Abstract
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 Ku-modulated two-ended versus one-ended chromosome break model is presented to explain these results.
摘要
哺乳动物细胞中的染色体双链断裂（DSB）可通过同源定向修复（HDR）进行修复，即以同源序列作为修复模板，或通过非同源末端连接（NHEJ）进行修复，后者通常涉及DSB位点处的序列改变。为了表征这两种途径的相互关系，我们分析了NHEJ组分缺陷细胞中DSB的HDR情况。我们发现，在Ku70（-/-）、XRCC4（-/-）和DNA-PKcs（-/-）细胞中，HDR频率增强，其中在Ku70（-/-）细胞中的增加尤为显著。姐妹染色单体交换和基因靶向频率均不依赖于这些NHEJ蛋白。我们提出了一个由Ku调节的两端与一端染色体断裂模型来解释这些结果。
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