Szumiel Irena, Foray Nicolas
Centre for Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Warszawa, Poland.
Acta Biochim Pol. 2011;58(1):11-8. Epub 2011 Mar 15.
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.
在发生于DNA双链断裂（DSB）修复过程中的染色质蛋白翻译后修饰中，乙酰化起着重要作用。本综述列出了有关该过程的若干事实和假说。缺乏乙酰转移酶TIP60（60 kDa的HIV-Tat相互作用蛋白）活性会导致细胞的DSB修复存在缺陷。该酶以多聚体蛋白复合物的形式存在于细胞核中。TIP60依赖的ATM（共济失调毛细血管扩张症突变激酶）激活是对DNA断裂反应中的早期事件。其他重要的乙酰化修饰是组蛋白H4和γH2AX的乙酰化修饰。受损位点的正确重建对于细胞的存活以及预防可能影响其子细胞功能的遗传和表观遗传变化至关重要。最近，两种在DSB修复中具有先前未被怀疑功能的蛋白质已被确定在此过程中具有活性：阿尔茨海默病β-淀粉样前体蛋白（APP）及其结合伴侣FE65，即β-淀粉样前体结合蛋白。它们在神经元和非神经元细胞的DSB修复中的参与与乙酰转移酶复合物进行的乙酰化有关。异染色质蛋白1（HP1）也具有相同的功能。到目前为止，HP1和FE65复合物对TIP60的激活之间的关系（如果存在）仍未明确。
