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bioRxiv · 10.1101/2023.10.17.562808

Zinc-dependent Nucleosome Reorganization by PARP2

Maluchenko, N.·Saulina, A.·Geraskina, O.·Kotova, E.·Korovina, A.·Feofanov, A.·Studitsky, V.
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Abstract

Poly(ADP-ribose)polymerase 2 (PARP2) is a nuclear protein that acts as a DNA damage sensor; it recruits the repair enzymes to a DNA damage site and facilitates formation of the repair complex. Using single particle Forster resonance energy transfer microscopy and electrophoretic mobility shift assay (EMSA) we demonstrated that PARP2 forms complexes with a nucleosome containing different number of PARP2 molecules without altering conformation of nucleosomal DNA both in the presence and in the absence of Mg2+or Ca2+ions. In contrast, Zn2+ ions directly interact with PARP2 inducing a local alteration of the secondary structure of the protein and PARP2-mediated, reversible structural reorganization of nucleosomal DNA. AutoPARylation activity of PARP2 is enhanced by Mg2+ ions and modulated by Zn2+ ions: suppressed or enhanced depending on the occupancy of two functionally different Zn2+ binding sites. The data suggest that Zn2+/PARP2-induced nucleosome reorganization and transient changes in the concentration of the cations could modulate PARP2 activity and the DNA damage response. Significance StatementPARP2 recognizes and binds DNA damage sites, recruits the repair enzymes to these sites and facilitates formation of the repair complex. Zn2+-induced structural reorganization of nucleosomal DNA in the complex with PARP2, which is reported in the paper, could modulate the DNA damage response. The obtained data indicate the existence of specific binding sites of Mg2+ and Zn2+ ions in and/or near the catalytic domain of PARP2, which modulate strongly, differently and ion-specifically PARylation activity of PARP2, which is important for maintaining genome stability, adaptation of cells to stress, regulation of gene expression and antioxidant defense.

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Maluchenko, N., Saulina, A., Geraskina, O., Kotova, E., Korovina, A., Feofanov, A., Studitsky, V.. 2023-10-17. Zinc-dependent Nucleosome Reorganization by PARP2. https://doi.org/10.1101/2023.10.17.562808

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