Show simple item record

dc.contributor.authorJones, Men_US
dc.contributor.authorBeuron, Fen_US
dc.contributor.authorBorg, Aen_US
dc.contributor.authorNans, Aen_US
dc.contributor.authorEarl, CPen_US
dc.contributor.authorBriggs, DCen_US
dc.contributor.authorSnijders, APen_US
dc.contributor.authorBowles, Men_US
dc.contributor.authorMorris, EPen_US
dc.contributor.authorLinch, Men_US
dc.contributor.authorMcDonald, NQen_US
dc.date.accessioned2020-03-10T14:24:50Z
dc.date.issued2020-02-28en_US
dc.identifier.citationNature communications, 2020, 11 (1), pp. 1120 - ?en_US
dc.identifier.issn2041-1723en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3541
dc.identifier.eissn2041-1723en_US
dc.identifier.doi10.1038/s41467-020-14856-2en_US
dc.description.abstractThe structure-specific endonuclease XPF-ERCC1 participates in multiple DNA damage repair pathways including nucleotide excision repair (NER) and inter-strand crosslink repair (ICLR). How XPF-ERCC1 is catalytically activated by DNA junction substrates is not currently understood. Here we report cryo-electron microscopy structures of both DNA-free and DNA-bound human XPF-ERCC1. DNA-free XPF-ERCC1 adopts an auto-inhibited conformation in which the XPF helical domain masks the ERCC1 (HhH)2 domain and restricts access to the XPF catalytic site. DNA junction engagement releases the ERCC1 (HhH)2 domain to couple with the XPF-ERCC1 nuclease/nuclease-like domains. Structure-function data indicate xeroderma pigmentosum patient mutations frequently compromise the structural integrity of XPF-ERCC1. Fanconi anaemia patient mutations in XPF often display substantial in-vitro activity but are resistant to activation by ICLR recruitment factor SLX4. Our data provide insights into XPF-ERCC1 architecture and catalytic activation.en_US
dc.formatElectronicen_US
dc.format.extent1120 - ?en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectHumansen_US
dc.subjectXeroderma Pigmentosumen_US
dc.subjectFanconi Anemiaen_US
dc.subjectEndonucleasesen_US
dc.subjectDNA-Binding Proteinsen_US
dc.subjectDNAen_US
dc.subjectCryoelectron Microscopyen_US
dc.subjectBinding Sitesen_US
dc.subjectProtein Conformationen_US
dc.subjectStructure-Activity Relationshipen_US
dc.subjectMutationen_US
dc.subjectModels, Molecularen_US
dc.subjectProtein Multimerizationen_US
dc.subjectProtein Domainsen_US
dc.titleCryo-EM structures of the XPF-ERCC1 endonuclease reveal how DNA-junction engagement disrupts an auto-inhibited conformation.en_US
dc.typeJournal Article
dcterms.dateAccepted2020-02-05en_US
rioxxterms.versionofrecord10.1038/s41467-020-14856-2en_US
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0en_US
rioxxterms.licenseref.startdate2020-02-28en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfNature communicationsen_US
pubs.issue1en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Structural Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Structural Biology/Structural Electron Microscopy
pubs.publication-statusPublisheden_US
pubs.volume11en_US
pubs.embargo.termsNot knownen_US
icr.researchteamStructural Electron Microscopyen_US
dc.contributor.icrauthorMorris, Edwarden_US
dc.contributor.icrauthorBeuron, Fabienneen_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

http://creativecommons.org/licenses/by/4.0/
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/