Poly(ADP-ribose)polymerase 2 (PARP2) is a nuclear protein, DNA damage sensor and an emerging target for development of anti-cancer drugs. Previously it was discovered that PARP2 binds to nucleosomes; however, critical factors involved in this process remain unknown. We demonstrated that in the presence of Mg or Ca ions PARP2 forms complexes with a nucleosome containing different number of PARP2 molecules without altering conformation of nucleosomal DNA. In contrast, Zn ions directly interact with PARP2 inducing a local alteration of the secondary structure of the protein and PARP2-mediated, reversible structural reorganization of nucleosomes. WGR domain of PARP2 is the target for Zn ions since this domain contains two putative Znbinding sites, binds Zn ions and alone drives Zn-mediated reorganization of nucleosomes. Auto(poly-ADP-ribosylation) activity of PARP2 is enhanced by Mg ions and modulated by Zn ions: suppressed or enhanced depending on the occupancy of two functionally different zinc binding sites. The data suggest that transient changes in concentration of cations can differentially modulate PARP2 activity, local chromatin structure and the DNA damage response.