Maluchenko Natalya, Saulina Alexandra, Geraskina Olga, Kotova Elena, Korovina Anna, Armeev Grigoriy, Kirpichnikov Mikhail, Feofanov Alexey, Studitsky Vasily
Faculty of Biology, Lomonosov Moscow State University, Moscow, 119234, Russia.
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia.
Cell Mol Life Sci. 2025 Jun 30;82(1):267. doi: 10.1007/s00018-025-05785-8.
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.
聚（ADP - 核糖）聚合酶2（PARP2）是一种核蛋白、DNA损伤传感器，也是抗癌药物开发中一个新兴的靶点。此前已发现PARP2与核小体结合；然而，这一过程中涉及的关键因素仍不清楚。我们证明，在镁离子或钙离子存在的情况下，PARP2与含有不同数量PARP2分子的核小体形成复合物，而不会改变核小体DNA的构象。相比之下，锌离子直接与PARP2相互作用，导致蛋白质二级结构发生局部改变，并引发PARP2介导的核小体可逆结构重组。PARP2的WGR结构域是锌离子的作用靶点，因为该结构域包含两个假定的锌结合位点，能结合锌离子，并且单独就能驱动锌介导的核小体重组。PARP2的自身（聚ADP - 核糖基化）活性受到镁离子的增强作用，并受到锌离子的调节：根据两个功能不同的锌结合位点的占据情况，锌离子会抑制或增强PARP2的活性。这些数据表明，阳离子浓度的瞬时变化可以差异性地调节PARP2活性、局部染色质结构和DNA损伤反应。
