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dc.contributor.authorMueller, Karinen
dc.contributor.authorHayward, Roberten
dc.contributor.authorRajan, Rakeshen
dc.contributor.authorWhitehead, Meredithen
dc.contributor.authorCobb, Andrew Men
dc.contributor.authorAhmad, Sadiaen
dc.contributor.authorSun, Mengxien
dc.contributor.authorGoldberga, Ievaen
dc.contributor.authorLi, Ruien
dc.contributor.authorBashtanova, Ulianaen
dc.contributor.authorPuszkarska, Anna Men
dc.contributor.authorReid, Daviden
dc.contributor.authorBrooks, Rogeren
dc.contributor.authorSkepper, Jeremy Nen
dc.contributor.authorBordoloi, Jayantaen
dc.contributor.authorChow, Wing Yingen
dc.contributor.authorOschkinat, Hartmuten
dc.contributor.authorGroombridge, Alexen
dc.contributor.authorScherman, Orenen
dc.contributor.authorHarrison, James Aen
dc.contributor.authorVerhulst, Anjaen
dc.contributor.authorD'Haese, Patrick Cen
dc.contributor.authorNeedham, Lisa-Mariaen
dc.contributor.authorLee, Steven Fen
dc.contributor.authorShanahan, Catherine Men
dc.contributor.authorDuer, Melinda Jen
dc.date.accessioned2020-10-19T23:31:06Z
dc.date.available2020-10-19T23:31:06Z
dc.identifier.issn2211-1247
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/311690
dc.description.abstractBiomineralization of the extracellular matrix is an essential, regulated process. Inappropriate mineralization of bone and the vasculature has devastating effects on patient health, yet an integrated understanding of the chemical and cell biological processes that lead to mineral nucleation remains elusive. Here, we report that biomineralization of bone and the vasculature is associated with extracellular poly(ADP-ribose) synthesized by poly(ADPribose) polymerases in response to oxidative and/or DNA damage. We use ultrastructural methods to show poly(ADP-ribose) can form both calcified spherical particles, reminiscent of those found in vascular calcification, and biomimetically calcified collagen fibrils similar to bone. Importantly, inhibition of poly(ADP-ribose) biosynthesis in vitro and in vivo inhibits biomineralization, suggesting a therapeutic route for the treatment of vascular calcifications. We conclude that poly(ADP-ribose) plays a central chemical role in both pathological and physiological extracellular matrix calcification.
dc.publisherElsevier
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titlePoly(ADP-Ribose) Links the DNA Damage Response and Biomineralizationen
dc.typeArticle
prism.publicationNameCell Reportsen
dc.identifier.doi10.17863/CAM.58780
dcterms.dateAccepted2019-05-09en
rioxxterms.versionofrecord10.1016/j.celrep.2019.05.038en
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2019-05-09en
dc.contributor.orcidMueller, Karin [0000-0003-4693-8558]
dc.contributor.orcidReid, David [0000-0003-2464-5295]
dc.contributor.orcidScherman, Oren [0000-0001-8032-7166]
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idBritish Heart Foundation (PG/10/43/28390)
pubs.funder-project-idMRC (MR/J007692/1)
pubs.funder-project-idMRC (MR/M01066X/1)


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International