Knockdown of histone H1–5 gene affects the sensitivity of MRC-5 and HeLa cells to DNA damaging agents

Linker histone H1.5, encoded by the H1–5 gene, plays a key role in chromatin compaction and genome stability. However, its role in cellular responses to mutagens is still poorly understood. Here, we analyzed the genotoxic effects of the standard genotoxic drugs doxorubicin (DOX) and mitomycin C (MMC) at non-cytotoxic concentrations after 24 h of treatment in normal lung fibroblasts (MRC-5) and cervical carcinoma cells (HeLa) with H1–5 gene knockdown (KD). Using CRISPR-Cas9, we achieved significant repression of H1–5 expression. Alkaline DNA comet assay and cytokinesis-block micronucleus assay showed that H1–5 KD significantly increased spontaneous and mutagen-induced DNA and chromosome damage levels in both cell lines (p < 0.05). Our results suggest that H1–5 gene deficiency makes DNA more susceptible to genotoxic impact while its mechanistic role in occurrence of DNA and chromosome damage requires further elucidation.