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Publication : Requirement for PBAF in transcriptional repression and repair at DNA breaks in actively transcribed regions of chromatin.

First Author  Kakarougkas A Year  2014
Journal  Mol Cell Volume  55
Issue  5 Pages  723-32
PubMed ID  25066234 Mgi Jnum  J:319964
Mgi Id  MGI:6867129 Doi  10.1016/j.molcel.2014.06.028
Citation  Kakarougkas A, et al. (2014) Requirement for PBAF in transcriptional repression and repair at DNA breaks in actively transcribed regions of chromatin. Mol Cell 55(5):723-32
abstractText  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.
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