Plugged into the Ku-DNA hub: The NHEJ network

• Published in: Progress in biophysics and molecular biology Vol. 147; pp. 62 - 76
• Main Authors: Frit, Philippe, Ropars, Virginie, Modesti, Mauro, Charbonnier, Jean Baptiste, Calsou, Patrick
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2019; Elsevier
• Subjects: Amino Acid Motifs; Animals; Biochemistry, Molecular Biology; Conserved binding motifs; DNA - genetics; DNA - metabolism; DNA damage; DNA End-Joining Repair; DNA repair machineries; Double-strand breaks; Humans; Ku Autoantigen - metabolism; Life Sciences; NHEJ; Protein interactions network; DNA-PKcs; vWA; MRI; TdT; DNA damage; PNKP; Ku; FATC; Conserved binding motifs; ds; FAT, FRAP; Double-strand breaks; HEAT; NAP1L; DSB; Protein interactions network; PR65/A; XLF; PAXX; PI3K; EMSA; KBM; KD; CYREN; WS; BRCT; RAG1; DNA-PK; DNA repair machineries; IR; PBZ; CTD; Cryo-EM; TDP1; APLF; Top1, Top2; NHEJ; PIKK; FHA
• ISSN: 0079-6107; 1873-1732; 1873-1732
• DOI: 10.1016/j.pbiomolbio.2019.03.001

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.