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Updated: Jun 14, 2025

CD Spectroscopy to Study DNA-Protein Interactions
Published on: February 10, 2022
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.
Abstract:
HSP110 is a ubiquitous chaperone contributing to proteostasis. It has a disaggregation activity and can refold denatured proteins. It can regulate fundamental signaling pathways involved in oncogenesis, such as Wnt/β-catenin, NF-κB and STAT3 signaling pathways. In gastric and colorectal cancer, HSP110 has been detected in the nucleus, and nuclear expression has been associated with the resistance of cells to 5-FU chemotherapy. Nuclear translocation of HSP110 is promoted by the exposure of cells to DNA-damaging agents. In a previous work, we demonstrated that nuclear HSP110 participates in the NHEJ DNA repair pathway by facilitating the recruitment of DNA-PKcs to Ku70/80 heterodimers at the site of DNA double-strand breaks. In the present work, analysis of HSP110s' nuclear interactome revealed an enrichment of components from SWI/SNF chromatin remodeling complexes. We demonstrate that HSP110 is strongly associated with chromatin in temozolomide- and oxaliplatin-treated cells and directly interacts with the core subunit SMARCC2, thereby facilitating the assembly of SWI/SNF complexes. This work expands upon the role of HSP110, which regulates not only proteostasis but also the assembly of critical nuclear macromolecular complexes involved in the adaptive stress response.
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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