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dc.contributor.authorMueller, Karinen
dc.date.accessioned2019-05-13T23:31:21Z
dc.date.available2019-05-13T23:31:21Z
dc.identifier.issn2211-1247
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/292766
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(ADP-ribose) 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.description.sponsorshipIncludes BHF and EPSRC funding.
dc.publisherElsevier
dc.rightsAttribution 4.0 International (CC BY)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titlePoly(ADP-ribose) links the DNA damage response to biomineralizationen
dc.typeArticle
prism.endingPage3138.e13
prism.issueIdentifier11en
prism.publicationNameCell Reportsen
prism.startingPage3124
prism.volume27en
dc.identifier.doi10.17863/CAM.39923
dcterms.dateAccepted2019-05-09en
rioxxterms.versionofrecord10.1016/j.celrep.2019.05.038en
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2019-05-09en
dc.contributor.orcidMueller, Karin [0000-0003-4693-8558]
dc.identifier.eissn2211-1247
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idBritish Heart Foundation (via King's College London) (MKJTSIR)
pubs.funder-project-idNational Institute for Health Research (Unknown)
pubs.funder-project-idMRC (MR/M01066X/1)
pubs.funder-project-idEPSRC (EP/L027151/1)
pubs.funder-project-idEPSRC (EP/G037221/1)
pubs.funder-project-idBritish Heart Foundation (PG/10/43/28390)
pubs.funder-project-idMRC (MR/J007692/1)
cam.issuedOnline2019-06-11en
cam.orpheus.successMon Jun 29 08:57:57 BST 2020 - The item has an open VoR version.*
rioxxterms.freetoread.startdate2100-01-01


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