LAUSR

Significance Here, we report that the lncRNA MILIP is transcriptionally regulated by N-Myc and functions to promote DNA double-strand break repair in neuroblastoma cells. MILIP is distinguished from other lncRNAs implicated in DNA repair through its scaffolding role in Ku complex formation, a requisite step to initiate the nonhomologous end-joining pathway. Our findings substantiate the long-postulated role of N-Myc in regulating DNA repair in neuroblastoma cells and reveal the functional importance of MILIP in cell survival, proliferation, and resistance to genotoxic stress, with practical implications of MILIP targeting, alone and in combination with DNA-damaging therapeutics, for neuroblastoma treatment.