The phenomenon of nicotinamide adenine dinucleotide (NAD+)-dependent poly(ADP-ribosyl)ation catalyzed with PARP1 was discovered long time ago, but it is still unclear how this post-translational modification governs a multitude of cellular processes including DNA repair. When interacting with the damaged DNA, PARP1 catalyzes the synthesis of a long branched poly (ADP-ribose) polymer (PAR) by using NAD+ as a substrate. PAR can be attached to the acceptor amino acid residues of nuclear proteins or to PARP1 itself. This process leads to reorganization of the functional protein complexes involved in DNA repair. The aims of the present study were to investigate the role of poly (ADP-ribosyl)ation in regulation of base excision repair (BER), to search new targets of PARylation catalyzed with PARP1 and PARP2 and to analyze the modulation of PARPs activity by RNA binding proteins. Methods: Biochemical approaches, fluorescence titration methods, atomic force microscopy (AFM), light-scattering technique. Results: PARP1 interacts with BER proteins as well as with DNA intermediates of BER containing breaks or apurinic/apyrimidinic sites [1]. PARP1 and PARP2 activities regulate BER. The PARP1 activity is modulated by disordered RNA binding proteins such as YB-1 and FUS. YB-1 stimulates PARP1 activity [2]. The PARP-1/PAR/DNA system was reconstituted in vitro and the role of FUS was analyzed at the single molecule level [3]. The dissociation of FUS from mRNA, its recruitment at DNA damage sites through its binding to PAR, and the assembly of damaged DNA-rich compartments were demonstrated. PARG, an enzyme family that hydrolyses PAR, is sufficient to dissociate damaged DNA-rich compartments and PARG hydrolysis initiates the nucleocytoplasmic shuttling of FUS in cells. We anticipate that FUS facilitates a rapid DNA repair through the transient compartmentalization of DNA damages by FUS interaction with PAR. Conclusion: The results obtained show the key role of PARP1 in regulation of BER and the modulation of PARP1 activity by RNA binding proteins YB-1 and FUS. Funding: This work was supported by grant from RSF 19-14-00107 (study of PARPs activity modulation by RNA binding proteins) and by Russian State funded budget project of ICBFM SB RAS (АААА-А17-117020210022-4). References: [1] Moor NA, Lavrik OI. Protein-Protein Interactions in DNA Base Excision Repair. Biochemistry (Mosc) 2018, 83:411-422. [2] Alemasova EE, Naumenko KN, Kurgina TA, Anarbaev RO, Lavrik OI. The multifunctional protein YB-1 potentiates PARP1 activity and decreases the efficiency of PARP1 inhibitors. Oncotarget. 2018, 9:23349-23365. [3] Singatulina AS, Hamon L, Sukhanova MV, Desforges B, Joshi V, Bouhss A, Lavrik OI, Pastré D. PARP-1 activation directs FUS to DNA damage sites to form PARG-reversible compartments enriched in damaged DNA. Cell Rep. 2019, in press.