The occurrence of DNA double strand breaks (DSBs) in the nucleus provokes inits structural organization a large-scale alteration whose molecular basisis still mostly unclear. Here, we show that DSBs trigger preferentialassembly of nucleoproteins in human cellular fractions and that they mediatethe separation of large protein-DNA aggregates from aqueous solution. Theinteraction among the aggregative nucleoproteins presents a dynamiccondition that allows the effective interaction of nucleoproteins withexternal molecules like free ATP and facilitates intrinsic DNA end-joiningactivity. This aggregative organization is functionally coacervate-like.The key component is DNA-dependent protein kinase, DNA-PK, which can becharacterized as a DNA-specific aggregation factor as well as a nuclearscaffold/matrix-interactive factor. In the context of aggregation, thekinase activity of DNA-PK is essential for efficient DNA end-joining. Themassive and functional concentration of nucleoproteins on DNA in vitro mayrepresent a possible status of nuclear dynamics in vivo, which probablyincludes the DNA-PK-dependent response to multiple DSBs
