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dc.contributor.authorGouge, J
dc.contributor.authorSatia, K
dc.contributor.authorGuthertz, N
dc.contributor.authorWidya, M
dc.contributor.authorThompson, AJ
dc.contributor.authorCousin, P
dc.contributor.authorDergai, O
dc.contributor.authorHernandez, N
dc.contributor.authorVannini, A
dc.date.accessioned2016-10-26T16:31:44Z
dc.date.issued2015-12-03
dc.identifier.citationCell, 2015, 163 (6), pp. 1375 - 1387
dc.identifier.issn0092-8674
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/189
dc.identifier.eissn1097-4172
dc.identifier.doi10.1016/j.cell.2015.11.005
dc.description.abstractTFIIB-related factor 2 (Brf2) is a member of the family of TFIIB-like core transcription factors. Brf2 recruits RNA polymerase (Pol) III to type III gene-external promoters, including the U6 spliceosomal RNA and selenocysteine tRNA genes. Found only in vertebrates, Brf2 has been linked to tumorigenesis but the underlying mechanisms remain elusive. We have solved crystal structures of a human Brf2-TBP complex bound to natural promoters, obtaining a detailed view of the molecular interactions occurring at Brf2-dependent Pol III promoters and highlighting the general structural and functional conservation of human Pol II and Pol III pre-initiation complexes. Surprisingly, our structural and functional studies unravel a Brf2 redox-sensing module capable of specifically regulating Pol III transcriptional output in living cells. Furthermore, we establish Brf2 as a central redox-sensing transcription factor involved in the oxidative stress pathway and provide a mechanistic model for Brf2 genetic activation in lung and breast cancer.
dc.formatPrint
dc.format.extent1375 - 1387
dc.languageeng
dc.language.isoeng
dc.publisherCELL PRESS
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectSaccharomyces cerevisiae
dc.subjectRNA Polymerase III
dc.subjectTranscription Factor TFIIIB
dc.subjectDNA
dc.subjectCrystallography, X-Ray
dc.subjectSequence Alignment
dc.subjectSignal Transduction
dc.subjectAmino Acid Sequence
dc.subjectOxidation-Reduction
dc.subjectModels, Molecular
dc.subjectMolecular Sequence Data
dc.titleRedox Signaling by the RNA Polymerase III TFIIB-Related Factor Brf2.
dc.typeJournal Article
dcterms.dateAccepted2015-10-23
rioxxterms.versionofrecord10.1016/j.cell.2015.11.005
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2015-12
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCell
pubs.issue6
pubs.notesNo embargo
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/Vannini Group
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/Vannini Group
pubs.publication-statusPublished
pubs.volume163
pubs.embargo.termsNo embargo
icr.researchteamVannini Group
dc.contributor.icrauthorGuthertz, Nicolas
dc.contributor.icrauthorVannini, Alessandro


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