The effect of Hus1 on ionizing radiation sensitivity is associated with homologous recombination repair but is independent of nonhomologous end-joining

Mammalian Hus1 plays an important role in maintaining genomic integrity. Cells lacking mouse Hus1 are hypersensitive to DNA damage inducers including UV and camptothecin ( CPT). By using clonogenic assay, we show here that Hus1 deficient mouse cells are hypersensitive to ionizing radiation ( IR) compared with their Hus1-positive counterparts. However, these cells show similar induction levels and similar rejoining rates of DNA double strand breaks ( DSBs) following IR, indicating that the effect of Hus1 on cell radiosensitivity is independent of nonhomologous end-joining (NHEJ). By combining an I-SceI-induced-DNA DSBs system and a siRNA approach, we also show that knocking down Hus1 decreases the efficiency of homologous recombination repair ( HRR), which is associated with the cellular sensitivity to IR-induced killing. Together, these results indicate that the role of Hus1 affecting the sensitivity of cells to IR-induced killing is independent of NHEJ but might be linked to HRR.