Figure 1.

The DNA damage response and DNA repair. (A) Ionizing radiation results in DNA base damage, single-strand breaks, and double-strand breaks that are repaired using base excision repair (BER), single-strand break repair (SSBR), or double-strand break repair (DSBR), respectively. The types of DSBR include non-homologous end-joining (NHEJ), which can occur through all phases of the cell cycle, or homologous recombination (HR), which requires cells to have completed synthesis phase. (B) Table of DNA repair disorders (gene deficiencies) that are associated with clinical radiation sensitivity, and (C) cell survival curves of normal cells and cells with such DDR/DNA repair deficiency. Cells with defective DDR/DNA repair pathways are more sensitive to radiation injury, as exemplified by a narrow shoulder region of the survival curve and lower radiation dose to achieve lethality. (D) Cell survival curves highlighting the effect of targeted strategies directed at inhibiting the “back-up” repair pathway. An example of doubly deficient cells could be BRCA1/2 deficient tumor cells (loss of DSBR) and selective PARP inhibition (loss of SSBR).