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Updated: Jul 22, 2025

Real-time Observation of the DNA Strand Exchange Reaction Mediated by Rad51
Published on: February 13, 2019
Different SWI/SNF complexes coordinately promote R-loop- and RAD52-dependent transcription-coupled homologous
Carlota Davó-Martínez1, Angela Helfricht1, Cristina Ribeiro-Silva1
1Department of Molecular Genetics, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam 3015 GD, The Netherlands.
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.
Insights
Multiple SWI/SNF complexes, including BAF, PBAF, and ncBAF, are recruited to DNA double-strand breaks (DSBs) in active genes. These complexes facilitate homologous recombination and transcriptional silencing for efficient DNA repair.
Area of Science:
- Cellular biology
- Molecular biology
- Cancer research
Background:
- The SWI/SNF family of ATP-dependent chromatin remodeling complexes plays a critical role in DNA damage response.
- BAF, PBAF, and ncBAF are distinct SWI/SNF complexes differing in subunit composition.
- Homologous recombination is a key pathway for repairing double-strand breaks (DSBs) in transcriptionally active DNA.
Purpose of the Study:
- To investigate the specific roles of different SWI/SNF complexes in DNA double-strand break repair.
- To elucidate the mechanisms by which SWI/SNF complexes regulate transcription during DNA repair.
- To understand how SWI/SNF complexes facilitate homologous recombination and R-loop resolution.
Main Methods:
- Chromatin immunoprecipitation to assess recruitment of SWI/SNF complexes to DSBs.
- RNA sequencing to monitor transcriptional changes near DNA damage sites.
- Biochemical assays to study R-loop resolution and DNA repair factor recruitment.
Main Results:
- BAF, PBAF, and ncBAF subunits are rapidly recruited to DSBs in a transcription-dependent manner.
- PBAF and ncBAF complexes induce RNA polymerase II eviction for transcriptional silencing.
- BAF complexes, particularly ARID1A-containing ones, promote RNaseH1 and RAD52 recruitment for R-loop resolution and repair.
Conclusions:
- Distinct SWI/SNF complexes orchestrate DNA repair at actively transcribed genes through coordinated actions.
- These complexes facilitate homologous recombination, transcriptional silencing, and R-loop resolution for efficient DNA damage repair.
- Understanding SWI/SNF complex functions provides insights into cancer development and potential therapeutic strategies.
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