Serine ADP-ribosylation in Drosophila provides insights into the evolution of reversible ADP-ribosylation signalling
dc.contributor.author | Fontana, P | |
dc.contributor.author | Buch-Larsen, SC | |
dc.contributor.author | Suyari, O | |
dc.contributor.author | Smith, R | |
dc.contributor.author | Suskiewicz, MJ | |
dc.contributor.author | Schützenhofer, K | |
dc.contributor.author | Ariza, A | |
dc.contributor.author | Rack, JGM | |
dc.contributor.author | Nielsen, ML | |
dc.contributor.author | Ahel, I | |
dc.date.accessioned | 2023-06-08T11:16:27Z | |
dc.date.issued | 2023-06-02 | |
dc.date.updated | 2023-06-08T10:25:46Z | |
dc.description.abstract | In the mammalian DNA damage response, ADP-ribosylation signalling is of crucial importance to mark sites of DNA damage as well as recruit and regulate repairs factors. Specifically, the PARP1:HPF1 complex recognises damaged DNA and catalyses the formation of serine-linked ADP-ribosylation marks (mono-Ser-ADPr), which are extended into ADP-ribose polymers (poly-Ser-ADPr) by PARP1 alone. Poly-Ser-ADPr is reversed by PARG, while the terminal mono-Ser-ADPr is removed by ARH3. Despite its significance and apparent evolutionary conservation, little is known about ADP-ribosylation signalling in non-mammalian Animalia. The presence of HPF1, but absence of ARH3, in some insect genomes, including Drosophila species, raises questions regarding the existence and reversal of serine-ADP-ribosylation in these species. Here we show by quantitative proteomics that Ser-ADPr is the major form of ADP-ribosylation in the DNA damage response of Drosophila melanogaster and is dependent on the dParp1:dHpf1 complex. Moreover, our structural and biochemical investigations uncover the mechanism of mono-Ser-ADPr removal by Drosophila Parg. Collectively, our data reveal PARP:HPF1-mediated Ser-ADPr as a defining feature of the DDR in Animalia. The striking conservation within this kingdom suggests that organisms that carry only a core set of ADP-ribosyl metabolising enzymes, such as Drosophila, are valuable model organisms to study the physiological role of Ser-ADPr signalling. | en_GB |
dc.description.sponsorship | Japan Society for the Promotion of Science (JSPS) | en_GB |
dc.description.sponsorship | Novo Nordisk Foundation | en_GB |
dc.description.sponsorship | Danish Council of Independent Research | en_GB |
dc.description.sponsorship | Danish Cancer Society | en_GB |
dc.description.sponsorship | European Union Horizon 2020 | en_GB |
dc.description.sponsorship | Wellcome Trust | en_GB |
dc.description.sponsorship | Biotechnology and Biological Sciences Research Council (BBSRC) | en_GB |
dc.description.sponsorship | Ovarian Cancer Research Alliance | en_GB |
dc.description.sponsorship | Cancer Research UK | en_GB |
dc.format.extent | 3200- | |
dc.format.medium | Electronic | |
dc.identifier.citation | Vol. 14, article 3200 | en_GB |
dc.identifier.doi | https://doi.org/10.1038/s41467-023-38793-y | |
dc.identifier.grantnumber | S2802 | en_GB |
dc.identifier.grantnumber | NNF14CC0001 | en_GB |
dc.identifier.grantnumber | NNF13OC0006477 | en_GB |
dc.identifier.grantnumber | 0135-00096 A | en_GB |
dc.identifier.grantnumber | 2034-00311 A | en_GB |
dc.identifier.grantnumber | 2032-00311 A | en_GB |
dc.identifier.grantnumber | R325-A18824 | en_GB |
dc.identifier.grantnumber | EPIC-XS-823839 | en_GB |
dc.identifier.grantnumber | 101794 | en_GB |
dc.identifier.grantnumber | 210634 | en_GB |
dc.identifier.grantnumber | BB/R007195/1 | en_GB |
dc.identifier.grantnumber | 813369 | en_GB |
dc.identifier.grantnumber | C35050/A22284 | en_GB |
dc.identifier.uri | http://hdl.handle.net/10871/133318 | |
dc.identifier | ORCID: 0000-0001-8341-6439 (Rack, Johannes Gregor Matthias) | |
dc.identifier | ScopusID: 56715439800 (Rack, Johannes Gregor Matthias) | |
dc.language.iso | en | en_GB |
dc.publisher | Nature Research | en_GB |
dc.relation.url | https://doi.org/10.2210/pdb8adk/pdb | en_GB |
dc.relation.url | https://doi.org/10.2210/pdb8adj/pdb | en_GB |
dc.rights | © The Author(s) 2023. Open access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ | en_GB |
dc.title | Serine ADP-ribosylation in Drosophila provides insights into the evolution of reversible ADP-ribosylation signalling | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2023-06-08T11:16:27Z | |
dc.identifier.issn | 2041-1723 | |
exeter.article-number | 3200 | |
dc.description | This is the final version. Available on open access from Nature Research via the DOI in this record | en_GB |
dc.description | Data availability: The atomic coordinates included in the study have been deposited in the Protein Data Bank (PDB) with the following accession codes: apo dParg, 8ADK [https://doi.org/10.2210/pdb8adk/pdb]; dParg:PARGi complex, 8ADJ [https://doi.org/10.2210/pdb8adj/pdb]. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository96 with the dataset identifier PXD036512. Full images of the blots and gel as well as data used to generate graphs can be found in the Source data file. Source data are provided with this paper. | en_GB |
dc.description | Materials availability: All constructs generated in this study are available upon request and will be fulfilled by the Lead Contact with a completed Materials Transfer Agreement. | en_GB |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.journal | Nature Communications | en_GB |
dc.relation.ispartof | Nature Communications, 14(1) | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2023-05-16 | |
dc.rights.license | CC BY | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2023-06-02 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2023-06-08T11:08:05Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2023-06-08T11:16:33Z | |
refterms.panel | A | en_GB |
refterms.dateFirstOnline | 2023-06-02 |
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