title: A kinetic model of single-strand annealing for the repair of DNA double-strand breaks.
abstract: Ionising radiation induces different types of DNA damage, including single-strand breaks, double-strand breaks (DSB) and base damages. DSB are considered to be the most critical lesion to be repaired. The three main competitive pathways in the repair of DSB are non-homologous end joining (NHEJ), homologous recombination (HR) and single-strand annealing (SSA). SSA is a non-conservative repair pathway requiring direct repeat sequences for the repair process. In this work, a biochemical kinetic model is presented to describe the SSA repair pathway. The model consists of a system of non-linear ordinary differential equations describing the steps in the repair pathway. The reaction rates were estimated by comparing the model results with the experimental data for chicken DT40 cells exposed to 20 Gy of X-rays. The model successfully predicts the repair of the DT40 cells with the reaction rates derived from the 20-Gy X-ray experiment. The experimental data and the kinetic model show fast and slow DSB repair components. The half time and fractions of the slow and the fast components of the repair were compared for the model and the experiments. Mathematical and computational modelling in biology has played an important role in predicting biological mechanisms and stimulating future experimentation. The present model of SSA adds to the modelling of NHEJ and HR to provide a more complete description of DSB repair pathways.
authors.affiliation: Radiation Biophysics Group, Department of Oncology-Pathology, Karolinska Institutet, Stockholm SE 171 76, Sweden. reza.taleei@ki.se
authors.forename: Reza
authors.initials: R
authors.lastname: Taleei
authors.forename: Michael
authors.initials: M
authors.lastname: Weinfeld
authors.forename: Hooshang
authors.initials: H
authors.lastname: Nikjoo
mesh_terms: D003198:Computer Simulation; D004249:DNA Damage / Q000502:physiology*; D004260:DNA Repair / Q000502:physiology* / Q000528:radiation effects*; D007700:Kinetics; D018499:Linear Energy Transfer / Q000502:physiology; D008956:Models, Chemical; D008957:Models, Genetic; D009010:Monte Carlo Method; D011829:Radiation Dosage