PARP Power: A Structural Perspective on PARP1, PARP2, and PARP3 in DNA Damage Repair and Nucleosome Remodelling
| العنوان: | PARP Power: A Structural Perspective on PARP1, PARP2, and PARP3 in DNA Damage Repair and Nucleosome Remodelling |
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| المؤلفون: | Éilís McClay, Marianne Schimpl, Laura Spagnolo, Taiana Maia de Oliveira, Saleha Patel, Lotte van Beek |
| المصدر: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 22, Iss 5112, p 5112 (2021) |
| بيانات النشر: | MDPI, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Models, Molecular, DNA Repair, DNA damage, QH301-705.5, Poly ADP ribose polymerase, Poly (ADP-Ribose) Polymerase-1, Cell Cycle Proteins, Review, Poly(ADP-ribose) Polymerase Inhibitors, DNA damage response, PARP-DNA binding, Catalysis, Inorganic Chemistry, chemistry.chemical_compound, PARP1, Allosteric Regulation, Protein Domains, Nucleosome, Humans, Physical and Theoretical Chemistry, Binding site, Biology (General), Molecular Biology, QD1-999, poly (ADP-ribose) polymerases 1-3, Spectroscopy, Polymerase, nucleosome remodelling, biology, histone PARylation factor 1, Organic Chemistry, Nuclear Proteins, General Medicine, Computer Science Applications, Cell biology, Nucleosomes, PARP activation, Chemistry, chemistry, ADP-ribosylation, biology.protein, Poly(ADP-ribose) Polymerases, Carrier Proteins, DNA |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1422-0067 1661-6596 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5495ef2ddd77c5127b5a44351c130bffTest http://europepmc.org/articles/PMC8150716Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5495ef2ddd77c5127b5a44351c130bff |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14220067 16616596 |
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