Tankyrases Promote Homologous Recombination and Check Point Activation in Response to DSBs |
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| Authors: | Zita Nagy Alkmini Kalousi Audrey Furst Marc Koch Benoit Fischer Evi Soutoglou |
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| Institution: | 1. Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France;2. Institut National de la Santé et de la Recherche Médicale (INSERM), U964, Illkirch, France;3. Centre National de Recherche Scientifique (CNRS), UMR7104, Illkirch, France;4. Université de Strasbourg, Illkirch, France;The University of North Carolina at Chapel Hill, UNITED STATES |
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| 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. |
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