The non-homologous end-joining (NHEJ) pathway and homologous recombination (HR) pathway share the duty to safeguard the genome stability when the most toxic DNA double-strand breaks occur. It is a crucial decision for cells to choose which pathway to orchestrate, in that making a wrong choice can lead to detrimental repair outcomes . Therefore, efforts are taken to identify the cellular determinants involved in the regulation of these two pathways. In a recent study, Misteli and colleagues treated immortalized human fibroblasts with DSB-inducing agents and found a lncRNA named DDSR1 (DNA damage-sensitive RNA1) which was highly induced upon damage in an ATM and NF-κB dependent manner (Figure 2B) . Interestingly, p53 was not required for DDSR1 induction after DNA damage, but DDSR1 can largely regulate p53 target genes under stress conditions. Moreover, cell proliferation and DNA damage signaling were reduced in cells lacking DDSR1 . In order to investigate the underlying mechanism by which DDSR1 affects DNA repair, the authors applied DSB repair reporter cell lines and found that only the HR pathway was compromised in DDSR1-deficient cells. The authors also found a RNA binding protein hnRNPUL1 physically associating with DDSR1. HnRNPUL1 has been reported to promote DNA end resection in HR pathway . Thus, further analysis demonstrated that depletion of DDSR1 increased accumulation of BRCA1/RAP80 complex at sites of DNA damage to restrict DNA end resection . Given that induction of DDSR1 took several hours to occur, while recruitment of BRCA1/RAP80 to DNA damage sites happens within several minutes, DDSR1 could possibly have dual roles in regulating HR: at early stage, DDSR1 associates with BRCA1/RAP80 complex to prevent them binding to damaged chromatin. Subsequently, DDSR1 expression is increased by ATM and NF-κB to inhibit p53 target gene expression . This study highlights the multifaceted nature of lncRNAs in maintaining genome integrity, providing new insights onto the precise targeted therapy for cancer.