Kinetic model of DNA double-strand break repair in primary human fibroblasts exposed to low-LET irradiation with various dose rates
Here we demonstrate the results of kinetic modeilng of DNA double-strand breaks induction and repair and phosphorilated histone H2AX (γ-H2AX) and Rad51 foci formation in primary human fibroblasts exposed to low-LET ionizing radiation (IR). The model describes two major paths of DNA double-strand breaks repair: non-homologous end joining (NHEJ) and homologous recombination (HR) and considers interactions between DNA and several repair proteins (DNA-PKcs, ATM, Ku70/80, XRCC1, XRCC4, Rad51, RPA, etc.) using mass action equations and Michaelis-Menten kinetics. Experimental data on DNA rejoining kinetics and γ-H2AX and Rad51 foci formation in vicinity of double strand breaks in primary human fibroblasts exposed to low-LET IR with various dose rates and exposure times was utilized for training and statistical validation of the model.