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dc.contributor.authorFontana, P
dc.contributor.authorBuch-Larsen, SC
dc.contributor.authorSuyari, O
dc.contributor.authorSmith, R
dc.contributor.authorSuskiewicz, MJ
dc.contributor.authorSchützenhofer, K
dc.contributor.authorAriza, A
dc.contributor.authorRack, JGM
dc.contributor.authorNielsen, ML
dc.contributor.authorAhel, I
dc.date.accessioned2023-06-08T11:16:27Z
dc.date.issued2023-06-02
dc.date.updated2023-06-08T10:25:46Z
dc.description.abstractIn 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.sponsorshipJapan Society for the Promotion of Science (JSPS)en_GB
dc.description.sponsorshipNovo Nordisk Foundationen_GB
dc.description.sponsorshipDanish Council of Independent Researchen_GB
dc.description.sponsorshipDanish Cancer Societyen_GB
dc.description.sponsorshipEuropean Union Horizon 2020en_GB
dc.description.sponsorshipWellcome Trusten_GB
dc.description.sponsorshipBiotechnology and Biological Sciences Research Council (BBSRC)en_GB
dc.description.sponsorshipOvarian Cancer Research Allianceen_GB
dc.description.sponsorshipCancer Research UKen_GB
dc.format.extent3200-
dc.format.mediumElectronic
dc.identifier.citationVol. 14, article 3200en_GB
dc.identifier.doihttps://doi.org/10.1038/s41467-023-38793-y
dc.identifier.grantnumberS2802en_GB
dc.identifier.grantnumberNNF14CC0001en_GB
dc.identifier.grantnumberNNF13OC0006477en_GB
dc.identifier.grantnumber0135-00096 Aen_GB
dc.identifier.grantnumber2034-00311 Aen_GB
dc.identifier.grantnumber2032-00311 Aen_GB
dc.identifier.grantnumberR325-A18824en_GB
dc.identifier.grantnumberEPIC-XS-823839en_GB
dc.identifier.grantnumber101794en_GB
dc.identifier.grantnumber210634en_GB
dc.identifier.grantnumberBB/R007195/1en_GB
dc.identifier.grantnumber813369en_GB
dc.identifier.grantnumberC35050/A22284en_GB
dc.identifier.urihttp://hdl.handle.net/10871/133318
dc.identifierORCID: 0000-0001-8341-6439 (Rack, Johannes Gregor Matthias)
dc.identifierScopusID: 56715439800 (Rack, Johannes Gregor Matthias)
dc.language.isoenen_GB
dc.publisherNature Researchen_GB
dc.relation.urlhttps://doi.org/10.2210/pdb8adk/pdben_GB
dc.relation.urlhttps://doi.org/10.2210/pdb8adj/pdben_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.titleSerine ADP-ribosylation in Drosophila provides insights into the evolution of reversible ADP-ribosylation signallingen_GB
dc.typeArticleen_GB
dc.date.available2023-06-08T11:16:27Z
dc.identifier.issn2041-1723
exeter.article-number3200
dc.descriptionThis is the final version. Available on open access from Nature Research via the DOI in this recorden_GB
dc.descriptionData 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.descriptionMaterials 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.eissn2041-1723
dc.identifier.journalNature Communicationsen_GB
dc.relation.ispartofNature Communications, 14(1)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_GB
dcterms.dateAccepted2023-05-16
dc.rights.licenseCC BY
rioxxterms.versionVoRen_GB
rioxxterms.licenseref.startdate2023-06-02
rioxxterms.typeJournal Article/Reviewen_GB
refterms.dateFCD2023-06-08T11:08:05Z
refterms.versionFCDVoR
refterms.dateFOA2023-06-08T11:16:33Z
refterms.panelAen_GB
refterms.dateFirstOnline2023-06-02


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© 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/
Except where otherwise noted, this item's licence is described as © 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/