Biochemical journal, 2010-02, Vol.426 (3), p.365-371
2010
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Physical interaction between the histone acetyl transferase Tip60 and the DNA double-strand breaks sensor MRN complex
- Ist Teil von
- Biochemical journal, 2010-02, Vol.426 (3), p.365-371
- Ort / Verlag
- England: Portland Press
- Erscheinungsjahr
- 2010
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Chromatin modifications and chromatin-modifying enzymes are believed to play a major role in the process of DNA repair. The histone acetyl transferase Tip60 is physically recruited to DNA DSBs (double-strand breaks) where it mediates histone acetylation. In the present study, we show, using a reporter system in mammalian cells, that Tip60 expression is required for homology-driven repair, strongly suggesting that Tip60 participates in DNA DSB repair through homologous recombination. Moreover, Tip60 depletion inhibits the formation of Rad50 foci following ionizing radiation, indicating that Tip60 expression is necessary for the recruitment of the DNA damage sensor MRN (Mre11-Rad50-Nbs1) complex to DNA DSBs. Moreover, we found that endogenous Tip60 physically interacts with endogenous MRN proteins in a complex which is distinct from the classical Tip60 complex. Taken together, our results describe a physical link between a DNA damage sensor and a histone-modifying enzyme, and provide important new insights into the role and mechanism of action of Tip60 in the process of DNA DSB repair.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0264-6021eISSN: 1470-8728DOI: 10.1042/bj20091329Titel-ID: cdi_hal_primary_oai_HAL_hal_00479248v1
- Format
- –
- Schlagworte
- Acid Anhydride Hydrolases, Biochemistry, Molecular Biology, Blotting, Western, Cell Cycle Proteins - genetics, Cell Cycle Proteins - metabolism, Cell Line, Tumor, DNA Breaks, Double-Stranded - radiation effects, DNA Repair, DNA Repair Enzymes - genetics, DNA Repair Enzymes - metabolism, DNA-Binding Proteins - genetics, DNA-Binding Proteins - metabolism, HeLa Cells, Histone Acetyltransferases - genetics, Histone Acetyltransferases - metabolism, Histones - genetics, Histones - metabolism, Humans, Immunoprecipitation, Jurkat Cells, Life Sciences, Lysine Acetyltransferase 5, MRE11 Homologue Protein, Nuclear Proteins - genetics, Nuclear Proteins - metabolism, Protein Binding, Radiation, Ionizing, Recombination, Genetic, RNA Interference