Poly(ADP-ribose)polymerase 2 is zinc-dependent enzyme and nucleosome reorganizer
Abstract 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...
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| Format: | Article |
| Language: | English |
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Springer
2025-06-01
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| Series: | Cellular and Molecular Life Sciences |
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| Online Access: | https://doi.org/10.1007/s00018-025-05785-8 |
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| author | Natalya Maluchenko Alexandra Saulina Olga Geraskina Elena Kotova Anna Korovina Grigoriy Armeev Mikhail Kirpichnikov Alexey Feofanov Vasily Studitsky |
| author_facet | Natalya Maluchenko Alexandra Saulina Olga Geraskina Elena Kotova Anna Korovina Grigoriy Armeev Mikhail Kirpichnikov Alexey Feofanov Vasily Studitsky |
| author_sort | Natalya Maluchenko |
| collection | DOAJ |
| description | Abstract 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 Mg2+ or Ca2+ ions PARP2 forms complexes with a nucleosome containing different number of PARP2 molecules without altering conformation of nucleosomal DNA. 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 nucleosomes. WGR domain of PARP2 is the target for Zn2+ ions since this domain contains two putative Zn2+−binding sites, binds Zn2+ ions and alone drives Zn2+-mediated reorganization of nucleosomes. Auto(poly-ADP-ribosylation) activity of PARP2 is enhanced by Mg2+ ions and modulated by Zn2+ 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. Graphical abstract |
| format | Article |
| id | doaj-art-e8fad3f41ef14915ae8a3c771b512e98 |
| institution | Kabale University |
| issn | 1420-9071 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Springer |
| record_format | Article |
| series | Cellular and Molecular Life Sciences |
| spelling | doaj-art-e8fad3f41ef14915ae8a3c771b512e982025-08-20T03:37:23ZengSpringerCellular and Molecular Life Sciences1420-90712025-06-0182111810.1007/s00018-025-05785-8Poly(ADP-ribose)polymerase 2 is zinc-dependent enzyme and nucleosome reorganizerNatalya Maluchenko0Alexandra Saulina1Olga Geraskina2Elena Kotova3Anna Korovina4Grigoriy Armeev5Mikhail Kirpichnikov6Alexey Feofanov7Vasily Studitsky8Faculty of Biology, Lomonosov Moscow State UniversityFaculty of Biology, Lomonosov Moscow State UniversityFaculty of Biology, Lomonosov Moscow State UniversityFox Chase Cancer CenterFaculty of Biology, Lomonosov Moscow State UniversityFaculty of Biology, Lomonosov Moscow State UniversityFaculty of Biology, Lomonosov Moscow State UniversityFaculty of Biology, Lomonosov Moscow State UniversityFaculty of Biology, Lomonosov Moscow State UniversityAbstract 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 Mg2+ or Ca2+ ions PARP2 forms complexes with a nucleosome containing different number of PARP2 molecules without altering conformation of nucleosomal DNA. 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 nucleosomes. WGR domain of PARP2 is the target for Zn2+ ions since this domain contains two putative Zn2+−binding sites, binds Zn2+ ions and alone drives Zn2+-mediated reorganization of nucleosomes. Auto(poly-ADP-ribosylation) activity of PARP2 is enhanced by Mg2+ ions and modulated by Zn2+ 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. Graphical abstracthttps://doi.org/10.1007/s00018-025-05785-8PARP2Zn2+Mg2+AutoPARylationSpFRET microscopyEMSA |
| spellingShingle | Natalya Maluchenko Alexandra Saulina Olga Geraskina Elena Kotova Anna Korovina Grigoriy Armeev Mikhail Kirpichnikov Alexey Feofanov Vasily Studitsky Poly(ADP-ribose)polymerase 2 is zinc-dependent enzyme and nucleosome reorganizer Cellular and Molecular Life Sciences PARP2 Zn2+ Mg2+ AutoPARylation SpFRET microscopy EMSA |
| title | Poly(ADP-ribose)polymerase 2 is zinc-dependent enzyme and nucleosome reorganizer |
| title_full | Poly(ADP-ribose)polymerase 2 is zinc-dependent enzyme and nucleosome reorganizer |
| title_fullStr | Poly(ADP-ribose)polymerase 2 is zinc-dependent enzyme and nucleosome reorganizer |
| title_full_unstemmed | Poly(ADP-ribose)polymerase 2 is zinc-dependent enzyme and nucleosome reorganizer |
| title_short | Poly(ADP-ribose)polymerase 2 is zinc-dependent enzyme and nucleosome reorganizer |
| title_sort | poly adp ribose polymerase 2 is zinc dependent enzyme and nucleosome reorganizer |
| topic | PARP2 Zn2+ Mg2+ AutoPARylation SpFRET microscopy EMSA |
| url | https://doi.org/10.1007/s00018-025-05785-8 |
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