Figure 10.

Relationships between physiological and pathological DNA breaks and the pathways for their joining. The physiological forms of double-strand breakage occur in V(D)J recombination (mediated by RAG1 and RAG2) and in class switch recombination (the nuclease for this is not yet identified). One source of pathological breaks is free radicals generated from oxidative respiration. Pathological breaks are also caused by ionizing radiation. Ionizing radiation arises constantly as cosmic rays (hydrogen and helium nuclei) from solar sources generate showers of secondary cosmic rays (some of which are γ-rays). Ionizing radiation also arises from naturally occurring radionuclides in the earth. 72 During G0, G1, and early S phases of the cell cycle, pathological breaks are primarily repaired by NHEJ.