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dc.contributor.authorCornwell, Matthew Jen
dc.contributor.authorThomson, Graeme Jen
dc.contributor.authorCoates, Juliaen
dc.contributor.authorBelotserkovskaya, Rimmaen
dc.contributor.authorWaddell, Ian Den
dc.contributor.authorJackson, Stephenen
dc.contributor.authorGalanty, Yaronen
dc.date.accessioned2019-09-18T23:31:17Z
dc.date.available2019-09-18T23:31:17Z
dc.identifier.issn1554-8929
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/296973
dc.description.abstractThe Fanconi anemia pathway orchestrates the repair of DNA inter-strand crosslinks and stalled replication forks. A key step in this pathway is UBE2T and FANCL dependent monoubiquitylation of the FANCD2-FANCI complex. The Fanconi anemia pathway represents an attractive therapeutic target because activation of this pathway has been linked to chemotherapy resistance in several cancers. However, very few selective inhibitors of ubiquitin conjugation pathways are known to date. By using a high-throughput screen compatible assay, we have identified a small molecule inhibitor of UBE2T/FANCL-mediated FANCD2 monoubiquitylation that sensitizes cells to the DNA cross-linking agent, carboplatin.
dc.description.sponsorshipM.J.C was funded through the Cambridge PhD Training Programme in Chemical Biology and Molecular Medicine. Y.G is funded by Cancer Research UK, C6/A18796 and a Wellcome Trust Investigator Award to S.P.J. 206388/Z/17/Z. Research in the Jackson lab is funded by CRUK (C6/A18796) and the Wellcome Trust (206388/Z/17/Z), with core infrastructure funding from the Wellcome Trust (203144) and CRUK (C6946/A24843). Work in the CRUK Manchester Institute Drug Discovery Unit was funded by CRUK (Grant numbers C480/A1141 and C309/A8274).
dc.languageenen
dc.publisherAmerican Chemical Society (ACS)
dc.rightsAttribution 4.0 International (CC BY)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleSmall Molecule Inhibition of UBE2T/FANCL-mediated Ubiquitylation in the Fanconi Anemia Pathwayen
dc.typeArticle
prism.endingPage2154
prism.issueIdentifier10en
prism.publicationNameACS Chemical Biologyen
prism.startingPage2148
prism.volume14en
dc.identifier.doi10.17863/CAM.44014
dcterms.dateAccepted2019-09-16en
rioxxterms.versionofrecord10.1021/acschembio.9b00570en
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2019-09-16en
dc.contributor.orcidJackson, Stephen [0000-0001-9317-7937]
dc.contributor.orcidGalanty, Yaron [0000-0001-7167-9004]
dc.identifier.eissn1554-8937
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idCancer Research UK (A18796)
pubs.funder-project-idWellcome Trust (206388/Z/17/Z)
pubs.funder-project-idCancer Research UK (C6946/A24843)
pubs.funder-project-idWellcome Trust (203144/Z/16/Z)
cam.issuedOnline2019-09-16en
cam.orpheus.successThu Jan 30 10:38:21 GMT 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)