Tip60 in DNA damage response and growth control: many tricks in one HAT.
The Tip60 histone acetyltransferase is part of an evolutionarily conserved multisubunit complex, NuA4, which is recruited by many transcription factors to their target promoters, where it is thought to participate in histone acetylation and transcriptional activation. These transcription factors include tumor promoters and also tumor suppressors, such as p53, which links Tip60 to DNA damage responses. Tip60 also has transcription-independent roles in DNA damage responses. First, independently from NuA4, Tip60 binds the kinases ataxia-telangiectasia mutated (ATM) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and participates in their activation by DNA double-strand breaks. Second, NuA4 is recruited to the chromatin surrounding the breaks and, through a series of chromatin modifications, contributes to the dynamics of DNA repair. These molecular activities might endow Tip60 with multiple and potentially antagonistic biological functions.
Squatrito
Massimo
M
Department of Experimental Oncology, European Institute of Oncology (IEO), IFOM-IEO Campus, Milan 20139, Italy.
Gorrini
Chiara
C
Amati
Bruno
B
D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D051548:Histone Acetyltransferases / Q000378:metabolism*; D006801:Humans; D000074443:Lysine Acetyltransferase 5; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D025521:Tumor Suppressor Proteins; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5; C504740:NuA4 protein, S cerevisiae; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases