title: p8/nupr1 regulates DNA-repair activity after double-strand gamma irradiation-induced DNA damage.
abstract: The stress protein p8 is a small, highly basic, unfolded, and multifunctional protein. We have previously shown that most of its functions are exerted through interactions with other proteins, whose activities are thereby enhanced or repressed. In this work we describe another example of such mechanism, by which p8 binds and negatively regulates MSL1, a histone acetyl transferase (HAT)-associated protein, which in turn binds the DNA-damage-associated 53BP1 protein to facilitate DNA repair following DNA gamma-irradiation. Contrary to the HAT-associated activity, MSL1-dependent DNA-repair activity is almost completely dependent on 53BP1 expression. The picture that has emerged from our findings is that 53BP1 could be a scaffold that gets the HAT MSL1-dependent DNA-repair activity to the sites of DNA damage. Finally, we also found that, although p8 expression is transiently activated after gamma-irradiation, it is eventually submitted to sustained down-regulation, presumably to allow development of MSL1-associated DNA-repair activity. We conclude that interaction of MSL1 with 53BP1 brings MSL1-dependent HAT activity to the vicinity of damaged DNA. MSL1-dependent HAT activity, which is negatively regulated by the stress protein p8, induces chromatin remodeling and relaxation allowing access to DNA of the repair machinery.
authors: INSERM U.624, Stress Cellulaire, Case 915, Parc Scientifique et Technologique de Luminy, Marseille Cedex 9, France.
authors: Meritxell
authors: M
authors: Gironella
authors: Cedric
authors: C
authors: Malicet
authors: Carla
authors: C
authors: Cano
authors: Maria José
authors: MJ
authors: Sandi
authors: Tewfik
authors: T
authors: Hamidi
authors: Ricardo Martin Neme
authors: RM
authors: Tauil
authors: Mariela
authors: M
authors: Baston
authors: Pia
authors: P
authors: Valaco
authors: Silvia
authors: S
authors: Moreno
authors: Frederic
authors: F
authors: Lopez
authors: Jose Luis
authors: JL
authors: Neira
authors: Jean Charles
authors: JC
authors: Dagorn
authors: Juan Lucio
authors: JL
authors: Iovanna
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000502:physiology*; D002460:Cell Line; D049109:Cell Proliferation; D003114:Colony-Forming Units Assay; D053903:DNA Breaks, Double-Stranded / Q000528:radiation effects*; D004260:DNA Repair / Q000502:physiology*; D005720:Gamma Rays; D015870:Gene Expression / Q000235:genetics / Q000528:radiation effects; D006367:HeLa Cells; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D020349:Surface Plasmon Resonance; D014162:Transfection; D000071857:Tumor Suppressor p53-Binding Protein 1; D020798:Two-Hybrid System Techniques
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051548:Histone Acetyltransferases; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D000071857:Tumor Suppressor p53-Binding Protein 1; C491643:NUPR1 protein, human; C498301:TP53BP1 protein, human; C544740:MSL1 protein, human