HSP110 Regulates the Assembly of the SWI/SNF Complex

Océane Pointeau1, Manon Paccagnini1, Natalia Borges-Bonan1

  • 1Institut National de la Santé et de la Recherche Médicale (Inserm), Inserm CTM UMR1231, Université Bourgogne-Europe, 21000 Dijon, France.

Cells
|June 11, 2025
PubMed

Insights

Heat shock protein 110 (HSP110) aids DNA repair and chromatin remodeling. This chaperone protein interacts with SWI/SNF complexes, enhancing cellular adaptive stress responses.

Area of Science:

  • Molecular Biology
  • Cellular Stress Response
  • Cancer Biology

Background:

  • Heat shock protein 110 (HSP110) is a chaperone involved in proteostasis and regulating oncogenic signaling pathways.
  • Nuclear HSP110 expression correlates with chemoresistance in gastric and colorectal cancers and is induced by DNA-damaging agents.
  • Previous studies showed nuclear HSP110's role in Non-Homologous End Joining (NHEJ) DNA repair.

Purpose of the Study:

  • To investigate the nuclear interactome of HSP110 in response to DNA damage.
  • To elucidate the role of HSP110 in chromatin remodeling and adaptive stress responses.

Main Methods:

  • Nuclear proteome analysis to identify HSP110 interacting partners.
  • Chromatin association assays in cells treated with DNA-damaging agents (temozolomide, oxaliplatin).
  • Co-immunoprecipitation to confirm direct interaction between HSP110 and SWI/SNF components.

Main Results:

  • HSP110's nuclear interactome is enriched with components of SWI/SNF chromatin remodeling complexes.
  • HSP110 associates with chromatin upon exposure to temozolomide and oxaliplatin.
  • HSP110 directly interacts with SMARCC2, a core subunit of SWI/SNF, facilitating complex assembly.

Conclusions:

  • HSP110 plays a novel role in facilitating the assembly of SWI/SNF chromatin remodeling complexes.
  • This function expands the known roles of HSP110 beyond proteostasis to include the regulation of critical nuclear macromolecular complexes.
  • HSP110 is integral to the adaptive stress response by modulating chromatin structure and DNA repair pathways.

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