The Non-homologous End-Joining (NHEJ) Mathematical Model for the Repair of Double-Strand Breaks: II. Application to Damage Induced by Ultrasoft X Rays and Low-Energy Electrons

Abstract

We investigated the kinetics of simple and complex types of double-strand breaks (DSB) using our newly proposed mechanistic mathematical model for NHEJ DSB repair. For this purpose the simulated initial spectrum of DNA DSB, induced in an atomistic canonical model of B-DNA by low-energy single electron tracks, 100 eV to 4.55 keV, and the electrons generated by ultrasoft X rays (CK, AlK and TiK), were subjected to NHEJ repair processes. The activity elapsed time of sequentially independent steps of repair performed by proteins involved in NHEJ repair process were calculated for separate DSB. The repair kinetics of DSBs were computed and compared with published data on repair kinetics obtained by pulsed-field gel electrophoresis method. The comparison shows good agreement for V79-4 cells irradiated with ultrasoft X rays. The average times for the repair of simple and complex DSB confirm that double-strand break complexity is a potential explanation for the slow component of DSB repair observed in V79-4 cells irradiated by ultrasoft X rays.

DSB repair model for mammalian cells in early S and G1 phases of the cell cycle: Application to damage induced by ionizing radiation of different quality

“…The presynaptic processes include Ku70/80 detection of damage and DNA-PKcs recruitment and autophosphorylation [19,20]. The rate constants of the initial processes have been verified by comparison with experimental results [19,21]. The presynaptic processes are required for all types of DSB, while end processing after the synapsis is dependent on the type of damage.…”

“…For damage induced by photons and electrons, we and others have proposed independent models of NHEJ that predict the DSB repair kinetics fairly accurately [19][20][21]45]. In other studies, the PARTRAC Monte Carlo track structure simulation code was used to calculate the repair kinetics of nitrogen ions [46,47].…”

“…But it is for the first time we have explored mechanistic and quantitative models of DSB repair to shed light on the issue [10,18,19,21]. We published a mechanistic model of DSB repair kinetics for G1 and early S phases of the cell cycle [18].…”

Genome-based, mechanism-driven computational modeling of risks of ionizing radiation: The next frontier in genetic risk estimation?

“…Presumably a similar situation holds in the USA. Our group has conducted pilot studies on the use of genomic knowledge to address some of the problems in genetic risk estimation (e.g., [1,[37][38][39][40][41][42][43][44][45][46]) but a comprehensive and integrated framework has not yet been put in place; there is still a long way to go. Several others have published on the basic science and biophysical modeling aspects of some of the issues considered here and are discussed in the text.…”

“…Subsequently, Taleei et al [43] applied their model to examine the repair kinetics of simple and complex types of DSB breaks induced by ultrasoft X-rays and low energy electrons (see also [41]). Both low energy electron tracks (100 eV to 4.55 keV) and C K , Al K and Ti K ultrasoft X-rays were simulated using the updated version of the track structure KURBEC code.…”