Open Access
Open access
Nucleic Acids Research, volume 51, issue 17, pages 9055-9074

Different SWI/SNF complexes coordinately promote R-loop- and RAD52-dependent transcription-coupled homologous recombination

Carlota Davó-Martínez 1
Angela Helfricht 1
Cristina Ribeiro-Silva 1
Anja Raams 1
Maria Tresini 1
Sidrit Uruci 1
Wiggert A. van Cappellen 2
Nitika Taneja 1
Jeroen A.A. Demmers 3
Alex PINES 1
Arjan F Theil 1
Wim Vermeulen 1
H. Lans 1
Show full list: 13 authors
Publication typeJournal Article
Publication date2023-07-20
scimago Q1
wos Q1
SJR7.048
CiteScore27.1
Impact factor16.6
ISSN03051048, 13624962
Genetics
Abstract

The SWI/SNF family of ATP-dependent chromatin remodeling complexes is implicated in multiple DNA damage response mechanisms and frequently mutated in cancer. The BAF, PBAF and ncBAF complexes are three major types of SWI/SNF complexes that are functionally distinguished by their exclusive subunits. Accumulating evidence suggests that double-strand breaks (DSBs) in transcriptionally active DNA are preferentially repaired by a dedicated homologous recombination pathway. We show that different BAF, PBAF and ncBAF subunits promote homologous recombination and are rapidly recruited to DSBs in a transcription-dependent manner. The PBAF and ncBAF complexes promote RNA polymerase II eviction near DNA damage to rapidly initiate transcriptional silencing, while the BAF complex helps to maintain this transcriptional silencing. Furthermore, ARID1A-containing BAF complexes promote RNaseH1 and RAD52 recruitment to facilitate R-loop resolution and DNA repair. Our results highlight how multiple SWI/SNF complexes perform different functions to enable DNA repair in the context of actively transcribed genes.

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