Mathematical Modeling of the DNA Double-Strand Break Repair in Mammalian and Human Cells
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.
KeywordsDNA double-strand break repair Ionizing radiation Mathematical modeling
- Taleei R (2013) Modelling and calculation of DNA damage and repair in mammalian cells induced by ionizing radiation of different quality. Doctoral thesis, Department of Oncology-Pathology, Karolinska Institutet. StockholmGoogle Scholar