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Nuclear poly(A)-binding protein 1 is an ATM target and essential for DNA double-strand break repair

Opened Access Nuclear poly(A)-binding protein 1 is an ATM target and essential for DNA double-strand break repair

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Autor: Prados Carvajal, Rosario
Huertas Sánchez, Pablo
Gavish Izakson, Michal
Bhavana Velpula, Bhagya
Elkon, Ran
Departamento: Universidad de Sevilla. Departamento de Genética
Fecha: 2018
Tipo de documento: Artículo
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 (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...
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Tamaño: 4.682Mb
Formato: PDF

URI: https://hdl.handle.net/11441/74699

DOI: 10.1093/nar/gkx1240

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