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Article Dans Une Revue Biochemical Journal Année : 2010

Physical interaction between the histone acetyl transferase Tip60 and the DNA double strand breaks sensor MRN complex

Catherine Chailleux
  • Fonction : Auteur
Sandrine Tyteca
  • Fonction : Auteur
Christophe Papin
François Boudsocq
  • Fonction : Auteur
Nadine Puget
Céline Courilleau
  • Fonction : Auteur
Yvan Canitrot

Résumé

Chromatin modifications and chromatin modifying enzymes are believed to play a major role in the process of DNA repair. The Tip60 histone acetyl transferase is physically recruited to DNA double strand breaks (DSB) where it mediates histone acetylation. Here, 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 radiations, indicating that Tip60 expression is necessary for the recruitment of the DNA damage sensor MRN (Mre11, Rad50, Nbs1) complex to DNA DSB. 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.

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Dates et versions

hal-00479248 , version 1 (30-04-2010)

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Catherine Chailleux, Sandrine Tyteca, Christophe Papin, François Boudsocq, Nadine Puget, et al.. Physical interaction between the histone acetyl transferase Tip60 and the DNA double strand breaks sensor MRN complex. Biochemical Journal, 2010, 426 (3), pp.365-371. ⟨10.1042/BJ20091329⟩. ⟨hal-00479248⟩
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