SWI/SNF: Complex complexes in genome stability and cancer

DNA Repair (Amst). 2019 May;77:87-95. doi: 10.1016/j.dnarep.2019.03.007. Epub 2019 Mar 15.

Abstract

SWI/SNF complexes are among the most studied ATP-dependent chromatin remodeling complexes, mostly due to their critical role in coordinating chromatin architecture and gene expression. Mutations in genes encoding SWI/SNF subunits are frequently observed in a large variety of human cancers, suggesting that one or more of the multiple SWI/SNF functions protect against tumorigenesis. Chromatin remodeling is an integral component of the DNA damage response (DDR), which safeguards against DNA damage-induced genome instability and tumorigenesis by removing DNA damage through interconnected DNA repair and signaling pathways. SWI/SNF has been implicated in facilitating repair of double-strand breaks, by non-homologous end-joining as well as homologous recombination, and repair of helix-distorting DNA damage by nucleotide excision repair. Here, we review current knowledge on SWI/SNF activity in the DDR and discuss the potential of exploiting DDR-related vulnerabilities due to SWI/SNF dysfunction for precision cancer therapy.

Keywords: Cancer therapy; DNA damage response; Homologous recombination; Non-homologous end-joining; Nucleotide excision repair; SWI/SNF.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Chromatin Assembly and Disassembly
  • Chromosomal Proteins, Non-Histone / metabolism*
  • DNA Damage
  • Genomic Instability*
  • Humans
  • Neoplasms / genetics*
  • Neoplasms / metabolism

Substances

  • Chromosomal Proteins, Non-Histone