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 present evidence for novel roles of histone acetylases. The TIP60 histone acetylase purifies as a multimeric protein complex. Besides histone acetylase activity on chromatin, the TIP60 complex possesses ATPase, DNA helicase, and structural DNA binding activities. Ectopic expression of mutated TIP60 lacking histone acetylase activity results in cells with defective double-strand DNA break repair. Importantly, the resulting cells lose their apoptotic competence, suggesting a defect in the cells' ability to signal the existence 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.
Ikura
T
T
Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA.
Ogryzko
V V
VV
Grigoriev
M
M
Groisman
R
R
Wang
J
J
Horikoshi
M
M
Scully
R
R
Qin
J
J
Nakatani
Y
Y
D000123:Acetyltransferases / Q000378:metabolism*; D000199:Actins / Q000737:chemistry; D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects; D001426:Bacterial Proteins / Q000737:chemistry; D004247:DNA / Q000378:metabolism; D004265:DNA Helicases / Q000378:metabolism; D004260:DNA Repair; D004591:Electrophoresis, Polyacrylamide Gel; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D006801:Humans; D000074443:Lysine Acetyltransferase 5; D046911:Macromolecular Substances; D008970:Molecular Weight; D011506:Proteins / Q000737:chemistry / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins
D000199:Actins; D001426:Bacterial Proteins; D046911:Macromolecular Substances; D011506:Proteins; C061260:RuvB protein, Bacteria; D029701:Saccharomyces cerevisiae Proteins; D004247:DNA; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5; D000251:Adenosine Triphosphatases; D004265:DNA Helicases