Involvement of the TIP60 histone acetylase complex in DNA repair and apoptosis

It is well known that histone acetylases are important chromatin modifiers and that they play a central role in chromatin transcription. Here, we pres ent evidence for novel roles of histone acetylases. The TIP60 histone acety lase purifies as a multimeric protein complex. Besides histone acetylase ac tivity on chromatin, the TIP60 complex possesses ATPase, DNA helicase, and structural DNA binding activities. Ectopic expression of mutated TIP60 lack ing histone acetylase activity results in cells with defective double-stran d DNA break repair. Importantly, the resulting cells lose their apoptotic c ompetence, suggesting a defect in the cells' ability to signal the existenc e of DNA damage to the apoptotic machinery. These results indicate that the histone acetylase TIP60-containing complex plays a role in DNA repair and apoptosis.