Ku affects the CHK1-dependent G(2) checkpoint after ionizing radiation.
Ku affects the CHK1-dependent G(2) checkpoint after ionizing radiation.
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发表时间：
2002-11
期刊：
影响因子：
11.2
通讯作者：
Xiang Wang;Gloria C. Li;G. Iliakis;Ya Wang
中科院分区：
文献类型：
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作者：
Xiang Wang;Gloria C. Li;G. Iliakis;Ya Wang
哺乳动物细胞中DNA双链断裂的修复主要有两种途径：非同源末端连接（NHEJ）和同源重组修复（HRR）。在没有Ku的细胞中，非同源末端连接修复是缺乏的，而与野生型细胞相比，HRR在这些细胞中是高效的。其机制尚不清楚。我们以前报道过，在电离辐射后，Ku 80（-/-）细胞比Ku 80（+/+）细胞显示出更强的ATM依赖性S期检查点反应（IR; X-Y. Zhou等人，Oncogene，21：6377-6381，2002）。本研究还发现，与Ku 80（+/+）细胞相比，Ku 80（-/-）细胞在IR后也表现出更强的G（2）积累，且更强的G（2）检查点反应与ATM无关，但伴随着更高的CHK 1激酶活性。Chk 1反义寡核苷酸处理后，Ku 80（-/-）细胞对IR的敏感性增强，G（2）检查点反应减弱，提示Ku 80（-/-）细胞对IR的敏感性增强是CHK 1依赖性的，提示CHK 1依赖性的检查点反应有助于这种细胞高效的HRR。
There are two major pathways for repairing DNA double strand breaks in mammalian cells: nonhomologous end joining (NHEJ) and homologous recombination repair (HRR). The nonhomologous end joining repair is deficient in cells without Ku, whereas HRR is highly efficient in such cells compared with their wild-type counterparts. The mechanism remains unclear. We reported previously that Ku80(-/-) cells show a stronger ATM-dependent S-phase checkpoint response than Ku80(+/+) cells after ionizing radiation (IR; X-Y. Zhou et al., Oncogene, 21:6377-6381, 2002). We report in this study that Ku80(-/-) cells also show a much stronger G(2) accumulation than Ku80(+/+) cells after IR. The stronger G(2) checkpoint response in Ku80(-/-) cells is ATM independent but is accompanied with a higher activity of CHK1 kinase. Treatment with Chk1 antisense oligonucleotide abolishes the stronger G(2) checkpoint response and sensitizes Ku80(-/-) cells to IR. These data indicate that the stronger G(2) checkpoint response shown in Ku80(-/-) cells is CHK1 dependent and suggest that the CHK1-dependent checkpoint response contributes to the highly efficient HRR in such cells.