Artículo
Nuclear poly(A)-binding protein 1 is an ATM target and essential for DNA double-strand break repair
Autor/es | Prados Carvajal, Rosario
Huertas Sánchez, Pablo Gavish Izakson, Michal Bhavana Velpula, Bhagya Elkon, Ran |
Departamento | Universidad de Sevilla. Departamento de Genética |
Fecha de publicación | 2018 |
Fecha de depósito | 2018-05-16 |
Publicado en |
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Resumen | The DNA damage response (DDR) is an extensive signaling network that is robustly mobilized by DNA double-strand breaks (DSBs). The primary transducer of the DSB response is the protein kinase, ataxia-telangiectasia, mutated ... The DNA damage response (DDR) is an extensive signaling network that is robustly mobilized by DNA double-strand breaks (DSBs). The primary transducer of the DSB response is the protein kinase, ataxia-telangiectasia, mutated (ATM). Here, we establish nuclear poly(A)-binding protein 1 (PABPN1) as a novel target of ATM and a crucial player in the DSB response. PABPN1 usually functions in regulation of RNA processing and stability. We establish that PABPN1 is recruited to the DDR as a critical regulator of DSB repair. A portion of PABPN1 relocalizes to DSB sites and is phosphorylated on Ser95 in an ATM-dependent manner. PABPN1 depletion sensitizes cells to DSB-inducing agents and prolongs the DSB-induced G2/M cell-cycle arrest, and DSB repair is hampered by PABPN1 depletion or elimination of its phosphorylation site. PABPN1 is required for optimal DSB repair via both nonhomologous end-joining (NHEJ) and homologous recombination repair (HRR), and specifically is essential for efficient DNA-end resection, an initial, key step in HRR. Using mass spectrometry analysis, we capture DNA damage-induced interactions of phospho-PABPN1, including well-established DDR players as well as other RNA metabolizing proteins. Our results uncover a novel ATM-dependent axis in the rapidly growing interface between RNA metabolism and the DDR. |
Cita | Prados Carvajal, R., Huertas Sánchez, P., Gavish Izakson, M., Bhavana Velpula, . y Elkon, R. (2018). Nuclear poly(A)-binding protein 1 is an ATM target and essential for DNA double-strand break repair. Nucleic Acids Research, 46 (2), 730-747. |
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