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Title

The transcriptional histone acetyltransferase cofactor TRRAP associates with the MRN repair complex and plays a role in DNA double-strand break repair

Authors
Robert, Flavie
Hardy, Sara
Nagy, Zita
Baldeyron, Céline
Déry, Ugo
Masson, Jean-Yves
Papadopoulo, Dora
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Published in Molecular and Cellular Biology. 2006, vol. 26, no. 2, p. 402-12
Abstract Transactivation-transformation domain-associated protein (TRRAP) is a component of several multiprotein histone acetyltransferase (HAT) complexes implicated in transcriptional regulation. TRRAP was shown to be required for the mitotic checkpoint and normal cell cycle progression. MRE11, RAD50, and NBS1 (product of the Nijmegan breakage syndrome gene) form the MRN complex that is involved in the detection, signaling, and repair of DNA double-strand breaks (DSBs). By using double immunopurification, mass spectrometry, and gel filtration, we describe the stable association of TRRAP with the MRN complex. The TRRAP-MRN complex is not associated with any detectable HAT activity, while the isolated other TRRAP complexes, containing either GCN5 or TIP60, are. TRRAP-depleted extracts show a reduced nonhomologous DNA end-joining activity in vitro. Importantly, small interfering RNA knockdown of TRRAP in HeLa cells or TRRAP knockout in mouse embryonic stem cells inhibit the DSB end-joining efficiency and the precise nonhomologous end-joining process, further suggesting a functional involvement of TRRAP in the DSB repair processes. Thus, TRRAP may function as a molecular link between DSB signaling, repair, and chromatin remodeling.
Keywords ATP-Binding Cassette Transporters/genetics/metabolismAdaptor Proteins, Signal TransducingAnimalsCell Cycle Proteins/genetics/metabolismCell Line, TumorChromatin Assembly and DisassemblyChromatography, GelDNA DamageDNA RepairDNA Repair Enzymes/genetics/metabolismDNA-Binding Proteins/genetics/metabolismHistone Acetyltransferases/genetics/metabolismHumansMiceNuclear Proteins/genetics/metabolismProtein BindingRNA, Small Interfering/geneticsSpectrometry, Mass, Matrix-Assisted Laser Desorption-IonizationTranscription Factors/genetics/metabolismTranscription, GeneticP300-CBP Transcription Factors
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PMID: 16382133
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ROBERT, Flavie et al. The transcriptional histone acetyltransferase cofactor TRRAP associates with the MRN repair complex and plays a role in DNA double-strand break repair. In: Molecular and Cellular Biology, 2006, vol. 26, n° 2, p. 402-12. https://archive-ouverte.unige.ch/unige:43633

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Deposited on : 2014-12-17

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