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Article: Screen identifies DYRK1B network as mediator of transcription repression on damaged chromatin

TitleScreen identifies DYRK1B network as mediator of transcription repression on damaged chromatin
Authors
KeywordsDNA damage
transcription
DNA double-strand breaks
DNA repair
DYRK1B
Issue Date2020
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings of the National Academy of Sciences, 2020, v. 117 n. 29, p. 17019-17030 How to Cite?
AbstractDNA double-strand breaks (DSBs) trigger transient pausing of nearby transcription, an emerging ATM-dependent response that suppresses chromosomal instability. We screened a chemical library designed to target the human kinome for new activities that mediate gene silencing on DSB-flanking chromatin, and have uncovered the DYRK1B kinase as an early respondent to DNA damage. We showed that DYRK1B is swiftly and transiently recruited to laser-microirradiated sites, and that genetic inactivation of DYRK1B or its kinase activity attenuated DSB-induced gene silencing and led to compromised DNA repair. Notably, global transcription shutdown alleviated DNA repair defects associated with DYRK1B loss, suggesting that DYRK1B is strictly required for DSB repair on active chromatin. We also found that DYRK1B mediates transcription silencing in part via phosphorylating and enforcing DSB accumulation of the histone methyltransferase EHMT2. Together, our findings unveil the DYRK1B signaling network as a key branch of mammalian DNA damage response circuitries, and establish the DYRK1B–EHMT2 axis as an effector that coordinates DSB repair on transcribed chromatin.
Persistent Identifierhttp://hdl.handle.net/10722/285055
ISSN
2019 Impact Factor: 9.412
2015 SCImago Journal Rankings: 6.883
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorDong, C-
dc.contributor.authorWest, KL-
dc.contributor.authorTan, XY-
dc.contributor.authorLI, J-
dc.contributor.authorIshibashi, T-
dc.contributor.authorYu, CH-
dc.contributor.authorSy, SMH-
dc.contributor.authorLeung, JWC-
dc.contributor.authorHuen, MSY-
dc.date.accessioned2020-08-07T09:06:08Z-
dc.date.available2020-08-07T09:06:08Z-
dc.date.issued2020-
dc.identifier.citationProceedings of the National Academy of Sciences, 2020, v. 117 n. 29, p. 17019-17030-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/285055-
dc.description.abstractDNA double-strand breaks (DSBs) trigger transient pausing of nearby transcription, an emerging ATM-dependent response that suppresses chromosomal instability. We screened a chemical library designed to target the human kinome for new activities that mediate gene silencing on DSB-flanking chromatin, and have uncovered the DYRK1B kinase as an early respondent to DNA damage. We showed that DYRK1B is swiftly and transiently recruited to laser-microirradiated sites, and that genetic inactivation of DYRK1B or its kinase activity attenuated DSB-induced gene silencing and led to compromised DNA repair. Notably, global transcription shutdown alleviated DNA repair defects associated with DYRK1B loss, suggesting that DYRK1B is strictly required for DSB repair on active chromatin. We also found that DYRK1B mediates transcription silencing in part via phosphorylating and enforcing DSB accumulation of the histone methyltransferase EHMT2. Together, our findings unveil the DYRK1B signaling network as a key branch of mammalian DNA damage response circuitries, and establish the DYRK1B–EHMT2 axis as an effector that coordinates DSB repair on transcribed chromatin.-
dc.languageeng-
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org-
dc.relation.ispartofProceedings of the National Academy of Sciences-
dc.rightsProceedings of the National Academy of Sciences. Copyright © National Academy of Sciences.-
dc.subjectDNA damage-
dc.subjecttranscription-
dc.subjectDNA double-strand breaks-
dc.subjectDNA repair-
dc.subjectDYRK1B-
dc.titleScreen identifies DYRK1B network as mediator of transcription repression on damaged chromatin-
dc.typeArticle-
dc.identifier.emailYu, CH: chyu1@hku.hk-
dc.identifier.emailSy, SMH: mhsy@hku.hk-
dc.identifier.emailHuen, MSY: huen.michael@hku.hk-
dc.identifier.authorityYu, CH=rp01930-
dc.identifier.authorityHuen, MSY=rp01336-
dc.description.naturepostprint-
dc.identifier.doi10.1073/pnas.2002193117-
dc.identifier.pmid32611815-
dc.identifier.pmcidPMC7382216-
dc.identifier.scopuseid_2-s2.0-85088882316-
dc.identifier.hkuros312395-
dc.identifier.volume117-
dc.identifier.issue29-
dc.identifier.spage17019-
dc.identifier.epage17030-
dc.identifier.isiWOS:000553292900020-
dc.publisher.placeUnited States-
dc.identifier.issnl0027-8424-

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