Genomic DNA is constantly exposed to a variety of genotoxic stresses, and it is crucial for organisms to be equipped with mechanisms for repairing the damaged genome. Previously, it was demonstrated that the mammalian CST (CTC1-STN1-TEN1) complex, which was originally identified as a single-stranded DNA-binding trimeric protein complex essential for telomere maintenance, is required for survival in response to hydroxyurea (HU), which induces DNA replication fork stalling. It is still unclear, however, how the CST complex is involved in the repair of diverse types of DNA damage induced by oxidizing agents such as H₂O₂.

STN1 knockdown (KD) sensitized HeLa cells to high doses of H₂O₂. While H₂O₂-induced DNA strand breaks throughout the cell cycle, STN1 KD cells were as resistant as control cells to H₂O₂ treatment when challenged in the G1 phase of the cell cycle, but they were sensitive when exposed to H₂O₂ in S/G2/M phase. STN1 KD cells showed a failure of DNA synthesis and RAD51 foci formation upon H₂O₂ treatment. Chemical inhibition of RAD51 in shSTN1 cells did not exacerbate the sensitivity to H₂O₂, implying that the CST complex and RAD51 act in the same pathway. Collectively, our results suggest that the CST complex is required for maintaining genomic stability in response to oxidative DNA damage, possibly through RAD51-dependent DNA repair/protection mechanisms.