The preservation of genome integrity is essential for cell homeostasis. It is determined not only by accurate DNA replication, but also by mechanisms of repairing accidental lesions that occur in DNA. To prevent the harmful effect of DNA damage and maintain genome integrity, cells have developed several DNA repair mechanisms. DNA damage response (DDR) detects different types of DNA damage and activates cell cycle control, DNA repair pathways, apoptosis, senescence, and cell death [1]. The most deleterious type of DNA damage is DNA double-strand breaks (DSB). Cells use two major pathways to repair DSBs, the non-homologous end joining (NHEJ) and homologous recombination (HR) [2]. For a proper repair process, both pathways require several proteins, which cooperate to detect, signal, and repair DSBs.

The key player in signaling of DSB is the ataxia-telangiectasia mutated (ATM) kinase [3]. In response to DNA damaging agents, ATM kinase is activated, which leads to a cascade of kinase reactions regulating cell cycle, apoptosis, and DNA damage repair. ATM plays very prominent roles in DSB repair during all phases of the cell cycle. So far, many downstream target proteins of ATM kinase were identified, including: TP53, FANCD2, NFKBIA, BRCA1, CTIP, NBN (nibrin), TERF1, RAD9 and DCLRE1C [4]. Phosphorylation of substrates by ATM initiates cell-cycle arrest at G1/S, intra-S and G2/M checkpoints [5]. ATM interacts with the MRN complex in the early phase of the DSB detection. The highly conserved MRN complex contains the proteins MRE11 (MRE11 homolog, double strand break repair nuclease), RAD50 (RAD50 double strand break repair protein) and NBN (nibrin) [6] and is located to the site of DNA damage with the help of PARP1 [7]. ATM is also responsible for the initiation of apoptosis in cells that failed to repair damaged DNA [8].

The ATM kinase is encoded in humans by a gene located on the long arm of chromosome 11 (11q22.3). Mutations in both alleles of the ATM gene lead to the genetic disorder ataxia-telangiectasia (AT, Louis–Bar syndrome). The most characteristic manifestations of AT are neurological dysfunction (ataxia) and dilated blood vessels (telangiectasia). Additional AT features include immunodeficiency, genomic instability, and cancer predisposition. ATM deficient cells are characterized by defective DNA damage repair and sensitivity to ionizing radiation [9]. AT patients have a 100-fold increased risk of cancer compared with the general population [10].

Despite substantial knowledge of DNA repair processes, still several aspects of DNA damage detection and signaling are not fully understood. Growing evidence suggests that various ncRNAs, including lncRNAs, could play an important role in DNA damage response [11]. It was shown that lncRNAs can act as signals for integration of cellular information or function as decoys with the ability to sequester RNA-binding proteins. LncRNAs have also been shown to form platforms for protein complexes or guide proteins to reach the appropriate localization on the chromatin [12]. This suggests that lncRNAs could be important molecules involved in the detection, signaling and repair of DNA damage. So far, a few lncRNAs involved in DDR have been identified and characterized, among them only three ATM-dependent lncRNAs [13], [14], [15]. However, a genome-wide identification of lncRNAs induced by DNA damage in the ATM-dependent manner has been performed only in mice [13]. Since lncRNAs are poorly conserved between species, studies in humans are necessary.

In this study we used immortalized lymphoblastoid cell lines (LCLs) derived from AT patients with mutated ATM, and from healthy donors. We studied the expression profiles at 1 h and 8 h after irradiation, which allowed identification of IR-induced lncRNAs. The induction dynamics and ATM dependency were confirmed for selected lncRNAs. We observed that ATM-dependent IR-induced lncRNAs are often localized near genes involved in DDR and that they may be involved in regulation of those genes.