1. Mechanisms of Nucleosome Reorganization by PARP1.
- Author
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Maluchenko NV, Nilov DK, Pushkarev SV, Kotova EY, Gerasimova NS, Kirpichnikov MP, Langelier MF, Pascal JM, Akhtar MS, Feofanov AV, and Studitsky VM
- Subjects
- DNA Repair genetics, Gene Expression Regulation genetics, Histones genetics, Humans, Molecular Dynamics Simulation, Promoter Regions, Genetic genetics, Chromatin genetics, DNA-Binding Proteins genetics, Nucleosomes genetics, Poly (ADP-Ribose) Polymerase-1 genetics
- Abstract
Poly(ADP-ribose) polymerase 1 (PARP1) is an enzyme involved in DNA repair, chromatin organization and transcription. During transcription initiation, PARP1 interacts with gene promoters where it binds to nucleosomes, replaces linker histone H1 and participates in gene regulation. However, the mechanisms of PARP1-nucleosome interaction remain unknown. Here, using spFRET microscopy, molecular dynamics and biochemical approaches we identified several different PARP1-nucleosome complexes and two types of PARP1 binding to mononucleosomes: at DNA ends and end-independent. Two or three molecules of PARP1 can bind to a nucleosome depending on the presence of linker DNA and can induce reorganization of the entire nucleosome that is independent of catalytic activity of PARP1. Nucleosome reorganization depends upon binding of PARP1 to nucleosomal DNA, likely near the binding site of linker histone H1. The data suggest that PARP1 can induce the formation of an alternative nucleosome state that is likely involved in gene regulation and DNA repair.
- Published
- 2021
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