title: Chromatin acetylation, β-amyloid precursor protein and its binding partner FE65 in DNA double strand break repair.
abstract: Among post-translational modifications of chromatin proteins taking place in DNA double strand break (DSB) repair, acetylation plays a prominent role. This review lists several facts and hypotheses concerning this process. Lack of acetyltransferase TIP60 (HIV-Tat interacting protein of 60 kDa) activity results in cells with defective DSB repair. The enzyme is present in the nucleus in a multimeric protein complex. TIP60 dependent activation of ATM (ataxia telangiectasia mutated kinase) is an early event in the response to DNA breakage. Other important acetylations are those of histones H4 and γH2AX. Correct reconstruction of the damaged site is critical for survival and prevention of genetic and epigenetic changes in the cell that may affect the function of its daughter cells. Recently, two proteins with previously unsuspected functions in DSB repair have been identified as active in this process: Alzheimer β-amyloid precursor protein (APP) and its binding partner FE65, β-amyloid precursor binding protein. Their participation in DSB repair in both neuronal and non-neuronal cells is related to acetylation carried out by the acetyltransferase complex. The same function is ascribed to heterochromatin protein 1 (HP1). So far, the relations (if any) between TIP60 activation by HP1 and by the FE65 complex remain unidentified.
authors.affiliation: Centre for Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Warszawa, Poland. i.szumiel@ichtj.waw.pl
authors.forename: Irena
authors.initials: I
authors.lastname: Szumiel
authors.forename: Nicolas
authors.initials: N
authors.lastname: Foray
mesh_terms: D000107:Acetylation; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C091042:APBB1 protein, human; D016564:Amyloid beta-Protein Precursor; D002843:Chromatin; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D051548:Histone Acetyltransferases