PA1 cells containing a truncated DNA polymerase β protein are more sensitive to gamma radiation

Purpose: DNA polymerase beta (Pol beta) acts in the base excision repair (BER) pathway. Mutations in DNA polymerase beta (Pol beta) are associated with different cancers. A variant of Pole with a 97 amino acid deletion (Pol beta Delta), in heterozygous conditions with wild-type Pole, was identified in sporadic ovarian tumor samples. This study aims to evaluate the gamma radiation sensitivity of Pol beta Delta for possible target therapy in ovarian cancer treatment. Materials and Methods: Pol beta Delta cDNA was cloned in a GFP vector and transfected in PA1 cells. Stable cells (PA1Pol beta Delta) were treated with Co-60 sourced gamma-ray (0-15 Gy) to investigate their radiation sensitivity. The affinity of Pol beta Delta with DNA evaluated by DNA protein in silica docking experiments. Results: The result showed a statistically significant (p < 0.05) higher sensitivity towards radiation at different doses (0-15 Gy) and time-point (48-72 hours) for PA1Pol beta Delta cells in comparison with normal PA1 cells. Ten Gy of gamma radiation was found to be the optimal dose. Significantly more PA1Pol beta Delta cells were killed at this dose than PA1 cells after 48 hours of treatment via an apoptotic pathway. The in silico docking experiments revealed that Pol beta Delta has more substantial binding potential towards the dsDNA than wild-type Pole, suggesting a possible failure of BER pathway that results in cell death. Conclusion: Our study showed that the PA1Pol beta Delta cells were more susceptible than PA1 cells to gamma radiation. In the future, the potentiality of ionizing radiation to treat this type of cancer will be checked in animal models.

Automated summary

The study found that Pol beta Delta cells with a 97 amino acid deletion were more sensitive to gamma radiation and exhibited a higher rate of apoptosis compared to normal cells. In silico docking experiments also revealed that Pol beta Delta had a stronger binding potential to dsDNA, potentially leading to cell death.