# HSP110 Regulates the Assembly of the SWI/SNF Complex

## TL;DR

This study shows that HSP110, a chaperone protein, helps assemble SWI/SNF chromatin remodeling complexes in response to DNA damage.

## Contribution

The novel finding is that HSP110 directly interacts with SMARCC2 to facilitate SWI/SNF complex assembly.

## Key findings

- HSP110 is enriched in SWI/SNF chromatin remodeling complex components in the nucleus.
- HSP110 interacts with the core subunit SMARCC2 to aid complex assembly.
- HSP110's role extends beyond proteostasis to include nuclear macromolecular complex regulation.

## 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.