title: Tankyrases Promote Homologous Recombination and Check Point Activation in Response to DSBs.
abstract: DNA lesions are sensed by a network of proteins that trigger the DNA damage response (DDR), a signaling cascade that acts to delay cell cycle progression and initiate DNA repair. The Mediator of DNA damage Checkpoint protein 1 (MDC1) is essential for spreading of the DDR signaling on chromatin surrounding Double Strand Breaks (DSBs) by acting as a scaffold for PI3K kinases and for ubiquitin ligases. MDC1 also plays a role both in Non-Homologous End Joining (NHEJ) and Homologous Recombination (HR) repair pathways. Here we identify two novel binding partners of MDC1, the poly (ADP-ribose) Polymerases (PARPs) TNKS1 and 2. We find that TNKSs are recruited to DNA lesions by MDC1 and regulate DNA end resection and BRCA1A complex stabilization at lesions leading to efficient DSB repair by HR and proper checkpoint activation.
authors: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France.|Institut National de la Santé et de la Recherche Médicale (INSERM), U964, Illkirch, France.|Centre National de Recherche Scientifique (CNRS), UMR7104, Illkirch, France.|Université de Strasbourg, Illkirch, France.
authors: Zita
authors: Z
authors: Nagy
authors: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France.|Institut National de la Santé et de la Recherche Médicale (INSERM), U964, Illkirch, France.|Centre National de Recherche Scientifique (CNRS), UMR7104, Illkirch, France.|Université de Strasbourg, Illkirch, France.
authors: Alkmini
authors: A
authors: Kalousi
authors: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France.|Institut National de la Santé et de la Recherche Médicale (INSERM), U964, Illkirch, France.|Centre National de Recherche Scientifique (CNRS), UMR7104, Illkirch, France.|Université de Strasbourg, Illkirch, France.
authors: Audrey
authors: A
authors: Furst
authors: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France.|Institut National de la Santé et de la Recherche Médicale (INSERM), U964, Illkirch, France.|Centre National de Recherche Scientifique (CNRS), UMR7104, Illkirch, France.|Université de Strasbourg, Illkirch, France.
authors: Marc
authors: M
authors: Koch
authors: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France.|Institut National de la Santé et de la Recherche Médicale (INSERM), U964, Illkirch, France.|Centre National de Recherche Scientifique (CNRS), UMR7104, Illkirch, France.|Université de Strasbourg, Illkirch, France.
authors: Benoit
authors: B
authors: Fischer
authors: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France.|Institut National de la Santé et de la Recherche Médicale (INSERM), U964, Illkirch, France.|Centre National de Recherche Scientifique (CNRS), UMR7104, Illkirch, France.|Université de Strasbourg, Illkirch, France.
authors: Evi
authors: E
authors: Soutoglou
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D018797:Cell Cycle Proteins; D002460:Cell Line; D053903:DNA Breaks, Double-Stranded; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D059765:Homologous Recombination; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D051135:Rad51 Recombinase / Q000235:genetics / Q000378:metabolism; D038501:Tankyrases / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019313:BRCA1 Protein; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D051135:Rad51 Recombinase; D038501:Tankyrases; D015534:Trans-Activators; D044767:Ubiquitin-Protein Ligases; C540398:BABAM1 protein, human; C492913:BRCA1 protein, human; C413163:MDC1 protein, human; C486521:RNF8 protein, human; C437334:TNKS2 protein, human; C418109:TNKS protein, human; C495153:RAD51 protein, human