Mathematical modeling of the DNA double-strand break repair in mammalian and human cells

Abstract

A numerical model is offered to simulate the major pathways of DNA double-strand break. It provides a possible mechanistic explanation of the basic regularities of DSB processing by means of the non-homologous end-joining (NHEJ), homologous recombination (HR), single-strand annealing (SSA) and two alternative end-joining pathways. The model reproduces the time-courses of radiation-induced fluorescent foci specific to particular repair processes. It was tested for a wide spectrum of radiations with different linear energy transfer values ranged from 0.2 to 236 keV/µm. Using the proposed approach, we have reproduced several experimental data sets on γ-H2AX foci remaining in different types of cells including those defective in NHEJ, HR, or SSA functions. The results produced meet the hypothesis that the alternative end-joining pathways represented by micro-SSA and Alt-NHEJ can eliminate some amount of DSBs when classical NHEJ fails.