Nelson Glyn, Buhmann Matthias, von Zglinicki Thomas
Centre for Integrated Systems Biology of Ageing and Nutrition, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK.
Cell Cycle. 2009 Oct 15;8(20):3379-83. doi: 10.4161/cc.8.20.9857. Epub 2009 Oct 19.
Nuclear DNA damage foci indicate ongoing DNA damage response, which is the major inducer of cell cycle arrest, cellular senescence and apoptosis. 53BP1 is one central mediator of the DNA damage response and a component of active DNA damage foci. Using an AcGFP-53BP1c fluorescent fusion protein that quantitatively reports DNA damage, we show that the recruitment of 53BP1 into gammaH2A.X-containing DNA damage foci was inhibited at G(2)/M. This suggests a possible mechanism for cells to continue through the G(2) checkpoint with gammaH2A.X-flagged double strand breaks via inhibition of 53BP1-mediated DNA damage signalling.
核DNA损伤灶表明正在进行的DNA损伤反应，这是细胞周期停滞、细胞衰老和凋亡的主要诱导因素。53BP1是DNA损伤反应的一个核心介质，也是活性DNA损伤灶的一个组成部分。我们使用一种可定量报告DNA损伤的AcGFP-53BP1c荧光融合蛋白，发现53BP1在G(2)/M期被抑制进入含γH2A.X的DNA损伤灶。这提示了一种可能的机制，即细胞通过抑制53BP1介导的DNA损伤信号传导，带着γH2A.X标记的双链断裂继续通过G(2)期检查点。
