Koshkina Daria, Maluchenko Natalya, Nilov Dmitry, Lyubitelev Alexander, Korovina Anna, Pushkarev Sergey, Armeev Grigoriy, Kirpichnikov Mikhail, Studitsky Vasily, Feofanov Alexey
Faculty of Biology, Lomonosov Moscow State University, Moscow 119234, Russia.
Belozersky Institute of Physicochemical Biology, Lomonosov Moscow State University, Moscow 119234, Russia.
Cells. 2025 Aug 25;14(17):1309. doi: 10.3390/cells14171309.
Poly(ADP-ribose)polymerase 1 (PARP1) is an enzyme that interacts with chromatin during DNA repair and transcription processes; the molecular mechanisms of these processes remain to be determined. Previously, we have shown that PARP1 can bind to and reorganize nucleosomes using two modes of interaction with a mono-nucleosome, which are realized through PARP1 binding to the ends of linker DNA and to the nucleosome core. Here, it is shown that the latter mode of binding induces the reorganization of nucleosome structure and is more stable under the conditions of poly(ADP-ribosyl)ation (PARylation). The initial nucleosome structure is fully recovered after the dissociation of autoPARylated PARP1. The competition between PARP1 and linker histone H1.0 for binding to a nucleosome is mediated by the PARP1-H1.0 interaction and is affected by the length of linker DNA fragments. Longer linkers stabilize H1.0-nucleosome complexes, while shorter linkers facilitate displacement of H1.0 from the chromatosome by PARP1. PARylation removes both H1.0 and PARP1 from the complexes with nucleosomes. The data suggest that the H1.0 displacement from chromatin by PARP1 that is likely modulated by the density of nucleosomes might reduce chromatin compaction and facilitate access of PARP1-dependent DNA repair and transcription factors to nucleosome and inter-nucleosomal DNA.
聚(ADP - 核糖)聚合酶1(PARP1)是一种在DNA修复和转录过程中与染色质相互作用的酶;这些过程的分子机制仍有待确定。此前,我们已经表明PARP1可以通过与单核小体的两种相互作用模式结合并重组核小体,这两种模式是通过PARP1与连接子DNA末端以及核小体核心的结合来实现的。在此表明,后一种结合模式会诱导核小体结构的重组,并且在聚(ADP - 核糖基)化(PARylation)条件下更稳定。自身PAR化的PARP1解离后,初始核小体结构完全恢复。PARP1与连接子组蛋白H1.0在结合核小体时的竞争是由PARP1 - H1.0相互作用介导的,并受连接子DNA片段长度的影响。较长的连接子会稳定H1.0 - 核小体复合物,而较短的连接子则有助于PARP1将H1.0从染色质小体中置换出来。PARylation会从与核小体的复合物中去除H1.0和PARP1。这些数据表明,PARP1可能通过核小体密度调节从染色质中置换H1.0,这可能会降低染色质的压缩程度,并促进依赖PARP1的DNA修复和转录因子接近核小体和核小体间的DNA。