Mechanisms of Nucleosome Reorganization by PARP1
Abstract
:1. Introduction
2. Results
2.1. Experimental Approaches for Analysis of PARP1-Dependent Changes in Nucleosome Structure
2.2. Characterization of the Nucleosomes and PARP1–Nucleosome Complexes
2.3. PARP1 Forms Structurally Distinct Complexes with Core Nucleosomes
2.4. Nucleosomes Containing an Extended DNA Region Are Fully Reorganized Only after Binding of Three Molecules of PARP1
2.5. Interaction between Two PARP1 Molecules Bound to Double Strand DNA Breaks Can Induce Changes in the Structure of Nucleosomes: MD Simulations
3. Discussion
4. Materials and Methods
4.1. Purification of Proteins, DNA Templates and Nucleosomes
4.2. spFRET Experiments in Solution
4.3. EMSA (Electrophoretic Mobility Shift Assay) Experiments
4.4. Single Particle Fluorescence Intensity Analysis of Nucleosomes in the Gel
4.5. Western Blot (WB) Experiments
4.6. DNaseI Footprinting
4.7. Molecular Modeling
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
PARP1 | poly(ADP-ribose)polymerase 1 |
PAR | poly(ADP-ribose) |
MD | molecular dynamics |
FRET | Förster resonance energy transfer |
spFRET | single particle Förster resonance energy transfer |
EMSA | electrophoretic mobility shift assay |
Cy3 and Cy5 | fluorescent dyes cyanine 3 and cyanine 5 |
EPR | proximity ratio (FRET efficiency without correction for detection sensitivity and quantum yields of fluorophores) |
LN_P, LN_M, LN_D | nucleosomes with one 20 bp linker labeled with Cy3/Cy5 at positions 13/91 bp, 35/112 bp or 57/135 bp, respectively |
CN_P, CN_M, CN_D | core nucleosomes labeled with Cy3/Cy5 at positions 13/91 bp, 35/112 bp or 57/135 bp, respectively |
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Name | Nucleotide Sequence |
---|---|
CN_P_forward | 5′-CCCGGTTCGCGC[Cy3-dT]CCCGCCTTCCGTGTGTTGTCGTCTCTCGG-3′ |
CN_P_reverse | 5′-ACCCCAGGGACTTGAAGTAATAAGGACGGAGGGCCTCTTTCAACATCGATGCACGG[Cy5-dT]GGTTAG-3′ |
CN_M_forward | 5′-CCCGGTTCGCGCTCCCGCCTTCCGTGTGTTGTCG[Cy5-dT]CTCTCGG-3′ |
CN_M_reverse | 5′-ACCCCAGGGACTTGAAGTAATAAGGACGGAGGGCC[Cy3-dT]CTTTCAACATCGAT-3′ |
CN_D_forward | 5′-CCCGGTTCGCGCTCCCGCCTTCCGTGTGTTGTCGTCTCTCGGGCGTCTAAGTACGC[Cy3-dT]TAGGC-3′ |
CN_D_reverse | 5’-ACCCCAGGGACT[Cy5-dT]GAAGTAATAAGGACGGAGGGCCTCTTTC-3′ |
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Maluchenko, N.V.; Nilov, D.K.; Pushkarev, S.V.; Kotova, E.Y.; Gerasimova, N.S.; Kirpichnikov, M.P.; Langelier, M.-F.; Pascal, J.M.; Akhtar, M.S.; Feofanov, A.V.; et al. Mechanisms of Nucleosome Reorganization by PARP1. Int. J. Mol. Sci. 2021, 22, 12127. https://doi.org/10.3390/ijms222212127
Maluchenko NV, Nilov DK, Pushkarev SV, Kotova EY, Gerasimova NS, Kirpichnikov MP, Langelier M-F, Pascal JM, Akhtar MS, Feofanov AV, et al. Mechanisms of Nucleosome Reorganization by PARP1. International Journal of Molecular Sciences. 2021; 22(22):12127. https://doi.org/10.3390/ijms222212127
Chicago/Turabian StyleMaluchenko, Natalya V., Dmitry K. Nilov, Sergey V. Pushkarev, Elena Y. Kotova, Nadezhda S. Gerasimova, Mikhail P. Kirpichnikov, Marie-France Langelier, John M. Pascal, Md. Sohail Akhtar, Alexey V. Feofanov, and et al. 2021. "Mechanisms of Nucleosome Reorganization by PARP1" International Journal of Molecular Sciences 22, no. 22: 12127. https://doi.org/10.3390/ijms222212127