Domínguez-Bendala Juan, Masutani Mitsuko, McWhir Jim
Diabetes Research Institute, University of Miami, 1450 NW 10th Avenue, FL 33136, USA.
Cell Biol Int. 2006 Apr;30(4):389-93. doi: 10.1016/j.cellbi.2005.12.005. Epub 2006 Feb 28.
The viability of non-homologous end-joining (NHEJ)-defective mice suggests that homologous recombination (HR) might take over its role in DNA repair. To test this hypothesis, we examined gene targeting frequencies (TF) in DNA-PK(cs), Ku80 and poly(ADP-ribose) polymerase (PARP-1) nullizygous cells. We observed a 3-fold TF increase in PARP-1 knockout embryonic stem (ES) cells, which is consistent with the predicted role of PARP-1 as a switch between HR and NHEJ. To a lesser extent, such effect could be reproduced upon chemical inhibition of PARP-1. However, TF was not enhanced in Ku80- or DNA-PK(cs)-defective cells. Our study also suggests an unexpected involvement of DNA-PK(cs) in HR.
非同源末端连接（NHEJ）缺陷小鼠的生存能力表明，同源重组（HR）可能会取代其在DNA修复中的作用。为了验证这一假设，我们检测了DNA-PK（cs）、Ku80和聚（ADP-核糖）聚合酶（PARP-1）纯合缺失细胞中的基因靶向频率（TF）。我们观察到PARP-1基因敲除胚胎干细胞（ES）中的TF增加了3倍，这与PARP-1作为HR和NHEJ之间开关的预测作用一致。在较小程度上，PARP-1的化学抑制也能产生类似效果。然而，Ku80或DNA-PK（cs）缺陷细胞中的TF并未增强。我们的研究还表明，DNA-PK（cs）意外地参与了HR。
