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.

PubMed

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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