Differential roles of DNA double strand break repair pathways in response to X-ray, proton, and alpha-particle irradiation

The results showed increased sensitivity to X-ray and proton radiation in NHEJ, HR, and TMEJ repair-deficient cell lines compared to wild-type cells, with similar trends for both radiation types. Notably, Rad54-deficient cells showed slower resolution of 53BP1 foci after proton exposure, indicating increased reliance on HR for repairing proton-induced DSBs. Clonogenic survival assays revealed a relative biological effectiveness (RBE) of 4.6-5.8 for alpha-particles compared to protons and X-rays, confirming that alpha-particles are more effective at causing cell death. Our findings suggest that TMEJ is important for repairing DSBs caused by alpha-particles. This study highlights differences in repairing low LET versus high LET DNA damage, offering new insights for radiation biology and therapeutic strategies.