Dose-Dependent Shift in Relative Contribution of Homologous Recombination to DNA Repair after Low-LET Ionizing Radiation Exposure: Empirical Evidence and Numerical Simulation.

Understanding the relative contributions of different repair pathways to radiation-induced DNA damage responses remains a challenging issue in terms of studying the radiation injury endpoints. The comparative manifestation of homologous recombination (HR) after irradiation with different doses greatly determines the overall effectiveness of recovery in a dividing cell after irradiation, since HR is an error-free mechanism intended to perform the repair of DNA double-strand breaks (DSB) during S/G2 phases of the cell cycle. In this article, we present experimentally observed evidence of dose-dependent shifts in the relative contributions of HR in human fibroblasts after X-ray exposure at doses in the range 20-1000 mGy, which is also supported by quantitative modeling of DNA DSB repair. Our findings indicate that the increase in the radiation dose leads to a dose-dependent decrease in the relative contribution of HR in the entire repair process.