CONFORMATIONAL CHANGE OF NUCLEAR ARCHITECTURE IN RESPONSE TO IONIZING IRRADIATION

我们研究了人体细胞对电离辐射的反应机制。为此，我们分析了辐射诱导的核焦点的结构和动力学以及受损染色质的重组。我们发现，DNA损伤诱导RAD51的焦点形成需要DNA损伤诱导的组蛋白H_2AX从受损的染色质中释放组蛋白H_2A的变体。损伤染色质中H_2AX的释放分别受Tip60和UBC13对H_2AX的乙酰化和泛素化的调节。我们还发现，另一种H_2A变异体--组蛋白H_2AZ在诱导DNA损伤后从染色质中释放出来。

We examined the mechanism of human cellular response against ionizing irradiation. For this purpose, we analyzed the structure and dynamics of the radiation-induced nuclear foci and reorganization of damaged chromatin. We found that DNA damage-induced release of histone H2AX, a variant of histone H2A, from damaged chromatin is required for the DNA damage-induced focus formation of RAD51. The release of H2AX from damaged chromatin is regulated by acetylation and ubiquitination of H2AX by TIP60 and UBC13, respectively, We also found that histone H2AZ, another H2A variant, is released from chromatin after induction of DNA damage.