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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. (2014)
Requirement for PBAF in Transcriptional Repression and Repair at DNA Breaks in Actively Transcribed Regions of Chromatin.
In: Molecular cell, 55 (5)
Artikel, Bibliographie

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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: 2014
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: Bibliographie
Titel: Requirement for PBAF in Transcriptional Repression and Repair at DNA Breaks in Actively Transcribed Regions of Chromatin.
Sprache: Englisch
Publikationsjahr: 2014
Titel der Zeitschrift, Zeitung oder Schriftenreihe: Molecular cell
Jahrgang/Volume einer Zeitschrift: 55
(Heft-)Nummer: 5
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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.

Fachbereich(e)/-gebiet(e): 10 Fachbereich Biologie
10 Fachbereich Biologie > Radiation Biology and DNA Repair
Hinterlegungsdatum: 05 Aug 2014 07:06
Letzte Änderung: 03 Jul 2024 02:21
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