Requirement for PBAF in Transcriptional Repression and Repair at DNA Breaks in Actively Transcribed Regions of Chromatin
| Autor: | Kakarougkas, Andreas, Ismail, Amani, Chambers, Anna, Riballo, Queti, Herbert, Alex, Kunzel, Julia, Lobrich, Markus, Jeggo, Penny, Downs, Jessica |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Binding Sites
DNA End-Joining Repair DNA Repair Chromosomal Proteins Non-Histone DNA Breaks fungi Ubiquitination Nuclear Proteins Cell Biology Article DNA-Binding Proteins Histones enzymes and coenzymes (carbohydrates) Gene Expression Regulation QH0426 Cell Line Tumor Humans Phosphorylation Molecular Biology HeLa Cells Transcription Factors |
| Zdroj: | Molecular Cell |
| ISSN: | 1097-2765 |
| Popis: | Summary 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. Graphical Abstract Highlights • BAF180 contributes to double-strand break (DSB)-induced transcriptional silencing • Transcriptionally active DSBs are dependent on BAF180 for efficient repair • PcG complexes and ATM phosphorylation of BAF180 are required for these activities • Cancer-associated BAF180 mutants are unable to restore these functions Cells silence ongoing transcription in response to a neighboring DNA double-strand break. Kakarougkas et al. show that the PBAF chromatin remodeling complex is important for this event and that failure to silence transcription leads to a delay in repair. |
| Databáze: | OpenAIRE |
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