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.

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.

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