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Requirement for PBAF in Transcriptional Repression and Repair at DNA Breaks in Actively Transcribed Regions of Chromatin

Kakarougkas, Andreas ; Ismail, Amani ; Chambers, Anna L. ; Riballo, Enriqueta ; Herbert, Alex D. ; Künzel, Julia ; Löbrich, Markus ; Jeggo, Penny A. ; Downs, Jessica A. (2021)
Requirement for PBAF in Transcriptional Repression and Repair at DNA Breaks in Actively Transcribed Regions of Chromatin.
In: Molecular Cell, 2014, 55 (5)
doi: 10.26083/tuprints-00018938
Artikel, Zweitveröffentlichung, Verlagsversion

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Kurzbeschreibung (Abstract)

Actively transcribed regions of the genome are vulnerable to genomic instability. Recently, it was discovered that transcription is repressed in response to neighboring DNA double-strand breaks (DSBs). It is not known whether a failure to silence transcription flanking DSBs has any impact on DNA repair efficiency or whether chromatin remodelers contribute to the process. Here, we show that the PBAF remodeling complex is important for DSB-induced transcriptional silencing and promotes repair of a subset of DNA DSBs at early time points, which can be rescued by inhibiting transcription globally. An ATM phosphorylation site on BAF180, a PBAF subunit, is required for both processes. Furthermore, we find that subunits of the PRC1 and PRC2 polycomb group complexes are similarly required for DSB-induced silencing and promoting repair. Cancer-associated BAF180 mutants are unable to restore these functions, suggesting PBAF's role in repressing transcription near DSBs may contribute to its tumor suppressor activity.

Typ des Eintrags: Artikel
Erschienen: 2021
Autor(en): Kakarougkas, Andreas ; Ismail, Amani ; Chambers, Anna L. ; Riballo, Enriqueta ; Herbert, Alex D. ; Künzel, Julia ; Löbrich, Markus ; Jeggo, Penny A. ; Downs, Jessica A.
Art des Eintrags: Zweitveröffentlichung
Titel: Requirement for PBAF in Transcriptional Repression and Repair at DNA Breaks in Actively Transcribed Regions of Chromatin
Sprache: Englisch
Publikationsjahr: 2021
Publikationsdatum der Erstveröffentlichung: 2014
Verlag: Elsevier
Titel der Zeitschrift, Zeitung oder Schriftenreihe: Molecular Cell
Jahrgang/Volume einer Zeitschrift: 55
(Heft-)Nummer: 5
DOI: 10.26083/tuprints-00018938
URL / URN: https://tuprints.ulb.tu-darmstadt.de/18938
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Herkunft: Zweitveröffentlichungsservice
Kurzbeschreibung (Abstract):

Actively transcribed regions of the genome are vulnerable to genomic instability. Recently, it was discovered that transcription is repressed in response to neighboring DNA double-strand breaks (DSBs). It is not known whether a failure to silence transcription flanking DSBs has any impact on DNA repair efficiency or whether chromatin remodelers contribute to the process. Here, we show that the PBAF remodeling complex is important for DSB-induced transcriptional silencing and promotes repair of a subset of DNA DSBs at early time points, which can be rescued by inhibiting transcription globally. An ATM phosphorylation site on BAF180, a PBAF subunit, is required for both processes. Furthermore, we find that subunits of the PRC1 and PRC2 polycomb group complexes are similarly required for DSB-induced silencing and promoting repair. Cancer-associated BAF180 mutants are unable to restore these functions, suggesting PBAF's role in repressing transcription near DSBs may contribute to its tumor suppressor activity.

Status: Verlagsversion
URN: urn:nbn:de:tuda-tuprints-189384
Sachgruppe der Dewey Dezimalklassifikatin (DDC): 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
Fachbereich(e)/-gebiet(e): 10 Fachbereich Biologie
10 Fachbereich Biologie > Radiation Biology and DNA Repair
Hinterlegungsdatum: 06 Sep 2021 12:30
Letzte Änderung: 13 Sep 2021 06:35
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