**1. Introduction**

Throughout their lifespan organisms are constantly exposed to genotoxic agents, both exogenous and endogenous. A rough assessment has revealed that up to 70,000 DNA damage events occur per human cell per day [1]. Under these conditions, preserving cell genome integrity is one of the most important challenges faced by multicellular organisms. Notably, unrepaired DNA damage contributes to the appearance of a pathological mutation [2–4]. The maintenance of genome stability is achieved by the machineries associated with the DNA damage response (DDR) and the cell death pathways that carry out detection of DNA damage or a signal of its presence to orchestrate DNA repair and induce cell death upon massive DNA damage, respectively [5,6]. For a long time, it has been believed that RNA-binding proteins (RBPs) interfere indirectly with the DDR through post-transcriptional regulation of gene expression [7–10]. Nonetheless, more and more studies are revealing the direct functions of many RBPs in the presence of DNA damage, e.g., sensing, signalling, and repair [11–13]. In this regard, poly(ADP-ribose) polymerases (PARPs), which are DNA damage sensors, may provide the basis for the control of RBPs over DNA repair and accordingly aroused special interest recently [14–19]. Indeed, DNA damage followed by PARPs' activation is accompanied with protein poly(ADP-ribosyl)ation (PARylation) through covalent attachment of ADP-ribose moieties and

the formation of an ADP-ribose chain: poly(ADP-ribose) (PAR) [20–22]. PAR is a polymeric molecule that shares several features with RNA, including a high negative charge and structural diversity (size, chain length, and branching complexity) [23–25]. A large body of evidence suggests that many RBPs interact with PAR and/or undergo post-translational modification through PARylation during genotoxic stress [26,27]. Moreover, RBPs contain low-complexity regions with self-adhesive properties abundantly as compared to other proteins. Low-complexity domains (LCDs), also called intrinsically disordered regions, are considered key components of membrane-less assemblies such as DNA damage foci, P-bodies or stress granules formed under stressful conditions in the cell [28–31]. PAR, in turn, may serve as a scaffolding factor for these RBP-containing assemblies [16]. Just as many RBPs, fused in sarcoma (FUS) combines self-adhesive LCDs with multifunctional DNA/RNA-binding domains. FUS is involved in the regulation of RNA metabolism, including transcription, pre-mRNA splicing, mRNA transport and translation [32]. In addition to its role in RNA metabolism, FUS was recently implicated in the maintenance of DNA integrity in response to DNA damage [33,34]. In particular, FUS is mainly a nuclear protein [35] that interacts with DNA repair factors and is associated with DNA damage–induced formation of nuclear foci [17,36–40]. Nonetheless, the exact functions of FUS in DNA repair remain unclear. In this review, we highlight the role of FUS in the maintenance of genome integrity, focusing on PARylation events and on how the FUS–PAR interaction may be connected with DNA repair.
