August 18, 2000 | Tsuyoshi Ikura, Vasily V. Ogryzko, Mikhail Grigoriev, Regina Groisman, Jin Wang, Masami Horikoshi, Ralph Scully, Jun Qin, and Yoshihiro Nakatani
The TIP60 histone acetylase complex plays a critical role in DNA repair and apoptosis. This study demonstrates that the TIP60 complex, a multimeric protein with histone acetylase, ATPase, DNA helicase, and structural DNA binding activities, is essential for DNA damage repair and the regulation of apoptosis. Ectopic expression of a mutated TIP60 lacking histone acetylase activity results in cells with defective double-strand DNA break repair and loss of apoptotic competence, indicating that TIP60 is involved in signaling DNA damage to the apoptotic machinery. The TIP60 complex contains several subunits, including PAF400, which is common to both the TIP60 and PCAF complexes. Additionally, the complex includes RuvB-like proteins, β-actin, and actin-related proteins, which contribute to its ATPase and DNA helicase activities. The TIP60 complex also binds to structural DNA and exhibits DNA helicase activity, suggesting its involvement in DNA repair processes. The study further shows that the TIP60 complex is necessary for efficient DNA repair and that its dysfunction leads to impaired DNA repair and apoptosis. These findings highlight the importance of the TIP60 histone acetylase complex in maintaining genomic stability and cellular homeostasis.The TIP60 histone acetylase complex plays a critical role in DNA repair and apoptosis. This study demonstrates that the TIP60 complex, a multimeric protein with histone acetylase, ATPase, DNA helicase, and structural DNA binding activities, is essential for DNA damage repair and the regulation of apoptosis. Ectopic expression of a mutated TIP60 lacking histone acetylase activity results in cells with defective double-strand DNA break repair and loss of apoptotic competence, indicating that TIP60 is involved in signaling DNA damage to the apoptotic machinery. The TIP60 complex contains several subunits, including PAF400, which is common to both the TIP60 and PCAF complexes. Additionally, the complex includes RuvB-like proteins, β-actin, and actin-related proteins, which contribute to its ATPase and DNA helicase activities. The TIP60 complex also binds to structural DNA and exhibits DNA helicase activity, suggesting its involvement in DNA repair processes. The study further shows that the TIP60 complex is necessary for efficient DNA repair and that its dysfunction leads to impaired DNA repair and apoptosis. These findings highlight the importance of the TIP60 histone acetylase complex in maintaining genomic stability and cellular homeostasis.