Fe65 is required for Tip60-directed histone H4 acetylation at DNA strand breaks
| Autor: | Maria Stante, Fabiana Passaro, Tommaso Russo, Giuseppina Minopoli, Luigi Del Vecchio, Maddalena Raia |
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| Přispěvatelé: | Stante, Maria, Minopoli, Giuseppina, Passaro, Fabiana, Raia, M., DEL VECCHIO, Luigi, Russo, Tommaso |
| Rok vydání: | 2009 |
| Předmět: |
DNA Repair
DNA repair DNA damage Nerve Tissue Proteins Receptors Cell Surface Lysine Acetyltransferase 5 Histone H4 Histones Amyloid beta-Protein Precursor Mice Histone H2A Animals Adaptor Proteins Signal Transducing Histone Acetyltransferases Multidisciplinary biology DNA Breaks Nuclear Proteins Acetylation Histone acetyltransferase Biological Sciences Molecular biology Proliferating cell nuclear antigen Chromatin Protease Nexins Protein Transport biology.protein Trans-Activators DNA mismatch repair |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 106(13) |
| ISSN: | 1091-6490 |
| Popis: | Fe65 is a binding partner of the Alzheimer's β-amyloid precursor protein APP. The possible involvement of this protein in the cellular response to DNA damage was suggested by the observation that Fe65 null mice are more sensitive to genotoxic stress than WT counterpart. Fe65 associated with chromatin under basal conditions and its involvement in DNA damage repair requires this association. A known partner of Fe65 is the histone acetyltransferase Tip60. Considering the crucial role of Tip60 in DNA repair, we explored the hypothesis that the phenotype of Fe65 null cells depended on its interaction with Tip60. We demonstrated that Fe65 knockdown impaired recruitment of Tip60-TRRAP complex to DNA double strand breaks and decreased histone H4 acetylation. Accordingly, the efficiency of DNA repair was decreased upon Fe65 suppression. To explore whether APP has a role in this mechanism, we analyzed a Fe65 mutant unable to bind to APP. This mutant failed to rescue the phenotypes of Fe65 null cells; furthermore, APP/APLP2 suppression results in the impairment of recruitment of Tip60-TRRAP complex to DNA double strand breaks, decreased histone H4 acetylation and repair efficiency. On these bases, we propose that Fe65 and its interaction with APP play an important role in the response to DNA damage by assisting the recruitment of Tip60-TRRAP to DNA damage sites. |
| Databáze: | OpenAIRE |
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