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dc.contributor.authorKitevski-LeBlanc, Julianne
dc.contributor.authorFradet-Turcotte, Amélie
dc.contributor.authorKukic, Predrag
dc.contributor.authorWilson, Marcus D
dc.contributor.authorPortella, Guillem
dc.contributor.authorYuwen, Tairan
dc.contributor.authorPanier, Stephanie
dc.contributor.authorDuan, Shili
dc.contributor.authorCanny, Marella D
dc.contributor.authorvan Ingen, Hugo
dc.contributor.authorArrowsmith, Cheryl H
dc.contributor.authorRubinstein, John L
dc.contributor.authorVendruscolo, Michele
dc.contributor.authorDurocher, Daniel
dc.contributor.authorKay, Lewis E
dc.date.accessioned2017-11-15T14:38:52Z
dc.date.available2017-11-15T14:38:52Z
dc.date.issued2017-04-13
dc.identifier.issn2050-084X
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/269292
dc.description.abstractSite-specific histone ubiquitylation plays a central role in orchestrating the response to DNA double-strand breaks (DSBs). DSBs elicit a cascade of events controlled by the ubiquitin ligase RNF168, which promotes the accumulation of repair factors such as 53BP1 and BRCA1 on the chromatin flanking the break site. RNF168 also promotes its own accumulation, and that of its paralog RNF169, but how they recognize ubiquitylated chromatin is unknown. Using methyl-TROSY solution NMR spectroscopy and molecular dynamics simulations, we present an atomic resolution model of human RNF169 binding to a ubiquitylated nucleosome, and validate it by electron cryomicroscopy. We establish that RNF169 binds to ubiquitylated H2A-Lys13/Lys15 in a manner that involves its canonical ubiquitin-binding helix and a pair of arginine-rich motifs that interact with the nucleosome acidic patch. This three-pronged interaction mechanism is distinct from that by which 53BP1 binds to ubiquitylated H2A-Lys15 highlighting the diversity in site-specific recognition of ubiquitylated nucleosomes.
dc.format.mediumElectronic
dc.languageeng
dc.publishereLife Sciences Publications, Ltd
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectHumans
dc.subjectUbiquitin-Protein Ligases
dc.subjectHistones
dc.subjectCryoelectron Microscopy
dc.subjectMagnetic Resonance Spectroscopy
dc.subjectProtein Binding
dc.subjectDNA Breaks, Double-Stranded
dc.subjectMolecular Dynamics Simulation
dc.titleThe RNF168 paralog RNF169 defines a new class of ubiquitylated histone reader involved in the response to DNA damage.
dc.typeArticle
prism.publicationDate2017
prism.publicationNameElife
prism.volume6
dc.identifier.doi10.17863/CAM.15491
dcterms.dateAccepted2017-04-12
rioxxterms.versionofrecord10.7554/eLife.23872
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2017-04-13
dc.contributor.orcidKitevski-LeBlanc, Julianne [0000-0002-6608-1187]
dc.contributor.orcidFradet-Turcotte, Amélie [0000-0002-5431-8650]
dc.contributor.orcidWilson, Marcus D [0000-0001-9551-5514]
dc.contributor.orcidYuwen, Tairan [0000-0003-3504-7995]
dc.contributor.orcidRubinstein, John L [0000-0003-0566-2209]
dc.contributor.orcidVendruscolo, Michele [0000-0002-3616-1610]
dc.contributor.orcidDurocher, Daniel [0000-0003-3863-8635]
dc.contributor.orcidKay, Lewis E [0000-0002-4054-4083]
dc.identifier.eissn2050-084X
rioxxterms.typeJournal Article/Review
pubs.funder-project-idEuropean Commission (654812)
cam.issuedOnline2017-04-13


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