Dynamics of TIP60 complex in the network of DNA damage response signaling

我们和其他研究小组已经表明，TIP60组蛋白乙酰转移酶复合物调节DNA损伤位点组蛋白H2AX和H4的超乙酰化，这对于高阶染色质改变至关重要。然而，目前尚不清楚TIP60的组装是如何在DNA损伤位点受到调节的。我们之前已经在纯化的TIP60复合体中鉴定了溴结构域蛋白BRDX。我们发现，细胞中BRDX的缺失会损害DNA损伤位点上TIP60的组装。这一发现表明BRDX是TIP60在DNA损伤位点组装所必需的。此外，我们发现TIP60对组蛋白H2AX的乙酰化是NBS1在DNA损伤位点保留所必需的。由于已有报道称TIP60具有抗癌信号分子的功能，我们现在正在研究通过TIP60- brdx复合物进行的染色质重组是否参与抗癌信号通路。

We and other group have shown that TIP60 histone acetyltransferase complex regulates hyperacetylation of histone H2AX and H4 at DNA damage sites, which is crucial for the higherorder chromatin alteration. However, it remains unclear how assembly of TIP60 is regulated at DNA damage sites. We have previosuly identified the bromodomain protein, BRDX, in the purified TIP60 complex. We found that the depletion of BRDX in cells impairs the assembly of TIP60 at DNA damage sites. This finding suggest that BRDX is required for the assembly of TIP60 at DNA damage sites. Moreover, we showed that the acetylation of histone H2AX by TIP60 is required for the retention of NBS1 at DNA damage sites. Since it has been reported that TIP60 functions as anti-cancer signaling molecule, we are now investigating whether chromatin reorganization via TIP60-BRDX complex is involved in the anti-cancer signaling pathway or not.