Gavish-Izakson, MichalVelpula, Bhagya BhavanaElkon, RanPrados-Carvajal, RosarioBarnabas, Georgina DUgalde, Alejandro PineiroAgami, ReuvenGeiger, TamarHuertas, PabloZiv, YaelShiloh, Yosef2023-01-252023-01-252018http://hdl.handle.net/10668/11921The 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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Ataxia Telangiectasia Mutated ProteinsCell Line, TumorDNADNA Breaks, Double-StrandedDNA RepairG2 Phase Cell Cycle CheckpointsHeLa CellsHumansNuclear ProteinsPhosphorylationPoly(A)-Binding Protein IProtein BindingProtein Interaction MapsRNA Interferenceresearch article29253183open access10.1093/nar/gkx12401362-4962PMC5778506https://academic.oup.com/nar/article-pdf/46/2/730/23595516/gkx1240.pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778506/pdf