Scientific article

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

Published inMolecular and cellular biology, vol. 26, no. 2, p. 402-412
Publication date2006

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.

  • ATP-Binding Cassette Transporters/genetics/metabolism
  • Adaptor Proteins, Signal Transducing
  • Animals
  • Cell Cycle Proteins/genetics/metabolism
  • Cell Line, Tumor
  • Chromatin Assembly and Disassembly
  • Chromatography, Gel
  • DNA Damage
  • DNA Repair
  • DNA Repair Enzymes/genetics/metabolism
  • DNA-Binding Proteins/genetics/metabolism
  • Histone Acetyltransferases/genetics/metabolism
  • Humans
  • Mice
  • Nuclear Proteins/genetics/metabolism
  • Protein Binding
  • RNA, Small Interfering/genetics
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Transcription Factors/genetics/metabolism
  • Transcription, Genetic
  • P300-CBP Transcription Factors
Affiliation Not a UNIGE publication
Citation (ISO format)
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. 402–412. doi: 10.1128/MCB.26.2.402-412.2006
Main files (1)
Article (Published version)
ISSN of the journal0270-7306

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