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Review

PARP Power: A Structural Perspective on PARP1, PARP2, and PARP3 in DNA Damage Repair and Nucleosome Remodelling

1
Structure and Biophysics, Discovery Sciences, R&D, AstraZeneca, Cambridge CB4 0WG, UK
2
Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, Garscube Campus, University of Glasgow, Glasgow G61 1QQ, UK
3
Discovery Biology, Discovery Sciences, R&D, AstraZeneca, Cambridge CB4 0WG, UK
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work
Academic Editor: Carlos Penedo
Int. J. Mol. Sci. 2021, 22(10), 5112; https://doi.org/10.3390/ijms22105112
Received: 6 April 2021 / Revised: 4 May 2021 / Accepted: 6 May 2021 / Published: 12 May 2021
Poly (ADP-ribose) polymerases (PARP) 1-3 are well-known multi-domain enzymes, catalysing the covalent modification of proteins, DNA, and themselves. They attach mono- or poly-ADP-ribose to targets using NAD+ as a substrate. Poly-ADP-ribosylation (PARylation) is central to the important functions of PARP enzymes in the DNA damage response and nucleosome remodelling. Activation of PARP happens through DNA binding via zinc fingers and/or the WGR domain. Modulation of their activity using PARP inhibitors occupying the NAD+ binding site has proven successful in cancer therapies. For decades, studies set out to elucidate their full-length molecular structure and activation mechanism. In the last five years, significant advances have progressed the structural and functional understanding of PARP1-3, such as understanding allosteric activation via inter-domain contacts, how PARP senses damaged DNA in the crowded nucleus, and the complementary role of histone PARylation factor 1 in modulating the active site of PARP. Here, we review these advances together with the versatility of PARP domains involved in DNA binding, the targets and shape of PARylation and the role of PARPs in nucleosome remodelling. View Full-Text
Keywords: Poly (ADP-ribose) polymerases 1-3; DNA damage response; PARP-DNA binding; ADP-ribosylation; nucleosome remodelling; histone PARylation factor 1; PARP activation Poly (ADP-ribose) polymerases 1-3; DNA damage response; PARP-DNA binding; ADP-ribosylation; nucleosome remodelling; histone PARylation factor 1; PARP activation
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MDPI and ACS Style

van Beek, L.; McClay, É.; Patel, S.; Schimpl, M.; Spagnolo, L.; Maia de Oliveira, T. PARP Power: A Structural Perspective on PARP1, PARP2, and PARP3 in DNA Damage Repair and Nucleosome Remodelling. Int. J. Mol. Sci. 2021, 22, 5112. https://doi.org/10.3390/ijms22105112

AMA Style

van Beek L, McClay É, Patel S, Schimpl M, Spagnolo L, Maia de Oliveira T. PARP Power: A Structural Perspective on PARP1, PARP2, and PARP3 in DNA Damage Repair and Nucleosome Remodelling. International Journal of Molecular Sciences. 2021; 22(10):5112. https://doi.org/10.3390/ijms22105112

Chicago/Turabian Style

van Beek, Lotte, Éilís McClay, Saleha Patel, Marianne Schimpl, Laura Spagnolo, and Taiana Maia de Oliveira. 2021. "PARP Power: A Structural Perspective on PARP1, PARP2, and PARP3 in DNA Damage Repair and Nucleosome Remodelling" International Journal of Molecular Sciences 22, no. 10: 5112. https://doi.org/10.3390/ijms22105112

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