Institut de Pharmacologie et Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, Toulouse, France; Equipe Labellisée Ligue Contre le Cancer, Toulouse, France.
Institute for Integrative Biology of the Cell (I2BC), Institute Joliot, CEA, CNRS, Univ. Paris-Sud, Université Paris-Saclay, 91198, Gif-sur-Yvette Cedex, France.
Prog Biophys Mol Biol. 2019 Oct;147:62-76. doi: 10.1016/j.pbiomolbio.2019.03.001. Epub 2019 Mar 6.
In vertebrates, double-strand breaks in DNA are primarily repaired by Non-Homologous End-Joining (NHEJ). The ring-shaped Ku heterodimer rapidly senses and threads onto broken DNA ends forming a recruiting hub. Through protein-protein contacts eventually reinforced by protein-DNA interactions, the Ku-DNA hub attracts a series of specialized proteins with scaffolding and/or enzymatic properties. To shed light on these dynamic interplays, we review here current knowledge on proteins directly interacting with Ku and on the contact points involved, with a particular accent on the different classes of Ku-binding motifs identified in several Ku partners. An integrated structural model of the core NHEJ network at the synapsis step is proposed.
在脊椎动物中,DNA 的双链断裂主要通过非同源末端连接 (NHEJ) 进行修复。环形 Ku 异二聚体快速感应并穿过断裂的 DNA 末端形成一个招募中心。通过蛋白质-蛋白质接触,最终通过蛋白质-DNA 相互作用加强,Ku-DNA 中心吸引一系列具有支架和/或酶活性的特异性蛋白质。为了阐明这些动态相互作用,我们在这里回顾了直接与 Ku 相互作用的蛋白质以及涉及的接触点的现有知识,特别强调了在几个 Ku 伙伴中鉴定的不同类别的 Ku 结合基序。提出了在连接步骤的核心 NHEJ 网络的综合结构模型。