PARP power: a structural perspective on PARP1, PARP2, and PARP3 in DNA damage repair and nucleosome remodelling

van Beek, L., McClay, É., Patel, S., Schimpl, M., Spagnolo, L. and Maia de Oliveira, T. (2021) PARP power: a structural perspective on PARP1, PARP2, and PARP3 in DNA damage repair and nucleosome remodelling. International Journal of Molecular Sciences, 22(10), 5112. (doi: 10.3390/ijms22105112) (PMID:34066057) (PMCID:PMC8150716)

Abstract

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Spagnolo, Professor Laura and McClay, Eilis

Creator Roles

McClay, É.: Writing – original draft, Writing – review and editing, Visualization, Formal analysis
Spagnolo, L.: Conceptualization, Writing – original draft, Writing – review and editing, Supervision

• Authors: van Beek, L., McClay, É., Patel, S., Schimpl, M., Spagnolo, L., and Maia de Oliveira, T.
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: International Journal of Molecular Sciences
• Publisher: MDPI
• ISSN: 1661-6596
• ISSN (Online): 1422-0067
• Published Online: 12 May 2021
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in International Journal of Molecular Sciences 22(10): 5112
• Publisher Policy: Reproduced under a Creative Commons License