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dc.contributor.authorSteurer, Barbara
dc.contributor.authorJanssens, Roel C
dc.contributor.authorGeijer, Marit E
dc.contributor.authorAprile-Garcia, Fernando
dc.contributor.authorGeverts, Bart
dc.contributor.authorTheil, Arjan F
dc.contributor.authorHummel, Barbara
dc.contributor.authorvan Royen, Martin E
dc.contributor.authorEvers, Bastiaan
dc.contributor.authorBernards, René
dc.contributor.authorHoutsmuller, Adriaan B
dc.contributor.authorSawarkar, Ritwick
dc.contributor.authorMarteijn, Jurgen
dc.date.accessioned2022-06-29T19:45:39Z
dc.date.available2022-06-29T19:45:39Z
dc.date.issued2022-06-24
dc.date.submitted2020-12-04
dc.identifier.issn2041-1723
dc.identifier.others41467-022-31329-w
dc.identifier.other31329
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/338508
dc.descriptionFunder: Oncode Institute
dc.description.abstractThe precise regulation of RNA Polymerase II (Pol II) transcription after genotoxic stress is crucial for proper execution of the DNA damage-induced stress response. While stalling of Pol II on transcription-blocking lesions (TBLs) blocks transcript elongation and initiates DNA repair in cis, TBLs additionally elicit a response in trans that regulates transcription genome-wide. Here we uncover that, after an initial elongation block in cis, TBLs trigger the genome-wide VCP-mediated proteasomal degradation of promoter-bound, P-Ser5-modified Pol II in trans. This degradation is mechanistically distinct from processing of TBL-stalled Pol II, is signaled via GSK3, and contributes to the TBL-induced transcription block, even in transcription-coupled repair-deficient cells. Thus, our data reveal the targeted degradation of promoter-bound Pol II as a critical pathway that allows cells to cope with DNA damage-induced transcription stress and enables the genome-wide adaptation of transcription to genotoxic stress.
dc.languageen
dc.publisherSpringer Science and Business Media LLC
dc.subjectArticle
dc.subject/631/1647/328/1978
dc.subject/631/337/4041/3196
dc.subject/631/337/1427/2566
dc.subject/631/337/572
dc.subject/13/1
dc.subject/13/109
dc.subject/13/95
dc.subject/14/19
dc.subject/14/35
dc.subject/38/35
dc.subjectarticle
dc.titleDNA damage-induced transcription stress triggers the genome-wide degradation of promoter-bound Pol II.
dc.typeArticle
dc.date.updated2022-06-29T19:45:38Z
prism.issueIdentifier1
prism.publicationNameNat Commun
prism.volume13
dc.identifier.doi10.17863/CAM.85921
dcterms.dateAccepted2022-06-10
rioxxterms.versionofrecord10.1038/s41467-022-31329-w
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidGeijer, Marit E [0000-0001-9453-6997]
dc.contributor.orcidAprile-Garcia, Fernando [0000-0002-5133-0857]
dc.contributor.orcidvan Royen, Martin E [0000-0002-6814-0996]
dc.contributor.orcidBernards, René [0000-0001-8677-3423]
dc.contributor.orcidMarteijn, Jurgen [0000-0001-9321-518X]
dc.identifier.eissn2041-1723
pubs.funder-project-idNederlandse Organisatie voor Wetenschappelijk Onderzoek (Netherlands Organisation for Scientific Research) (VI.C.182.025, 912.12.132, 864.13.004)
cam.issuedOnline2022-06-24


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