Figure 1.

Schematic representation of prominent pan-nuclear-acting (global) factors, global factors acting randomly at different sites, and site-specific (local) factors that participate in the selection of DSB repair pathways at individual DSB damage sites. (A) Left: definition of the nuclear competence of repair pathway-selecting factor types; the area of competence is indicated by the red frames. Right: DSB repair pathways plus their principles and mutual transitions depending on the cell cycle phase (G1 vs. S/G2 cells). (B) Examples of global factors (a–d) having a pancellular effect on DSB repair pathways and their selection. Repair pathways preferred or affected by each of these factors and the character of their influence are suggested. (C) The relationship between three interdependent factors related to irradiation that have a global mode of action but locally specific effects—radiation LET, irradiation conditions (dose, dose rate) and chromatin architecture (a–c)—is proposed, together with the potential outcomes of these factors on DSB repair pathway selection. (D) Diversity of radiation-induced DSB damage sites in terms of (a) the characteristics of broken DNA ends, the architecture and function of damaged chromatin (b), and the epigenetic code. The influence of these local factors on DSB repair pathways is indicated. For interactions between factors B, C and D and their joint effect on the activation of particular DSB repair pathways, see Figures 3 and 4.