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Chromatin regulator HELLS mediates SSB repair and responses to DNA alkylation damage

GSE283831 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2025/07/01 Platform GPL24676
Summary
The SNF2 family chromatin remodeler HELLS has emerged as an important regulator of cell proliferation, genome stability, and several cancer pathways. Significant upregulation of HELLS has been reported in 33 human cancer types. While HELLS has been implicated in DNA damage response, its function in DNA repair is poorly understood. Here we report a new regulatory link between HELLS and single-strand break (SSB) repair in cellular responses to DNA alkylation damage. We found that loss of HELLS impairs SSB repair, and selectively sensitizes cells to DNA alkylating agents and PARP inhibitors (PARPi). Furthermore, we found that HELLS is co-expressed with PARP1 in cancer cells, and its loss is synthetic lethal with homologous recombination deficiency (HRD). This work unveils new functions of HELLS in modulating SSB repair and responses to clinically relevant DNA alkylation damage, thus offering new insights into the potential therapeutic value of targeting HELLS in cancer.
Published in
The chromatin regulator HELLS mediates SSB repair and responses to DNA alkylation damage
Joseph JT, Wright CM, Peixoto E et al. · Nucleic acids research 2025 · PMID 41297801 · doi:10.1093/nar/gkaf1201
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Also filed as BioProject PRJNA1195851 and SRA study SRP550211. Searching any of these in the dataset finder brings you back here.

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