Radiation Dose Does Matter: Mechanistic Insights into DNA Damage and Repair Support the Linear No-Threshold Model of Low-Dose Radiation Health Risks

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FIGURE 1.
Overview of nonhomologous end joining (13). Schematic of a DNA DSB and its repair by NHEJ (top). Ku70–Ku80 heterodimer (Ku) binds to ends of DSB and improves subsequent binding by NHEJ polymerase, nuclease, and ligase complexes. These enzymes can act on ends of DSB in any order to resect and add nucleotides. Multiple rounds of resection and addition are possible. Nuclease and polymerase activities at each of the 2 DNA ends appear to be independent. Microhomology between the 2 DNA ends—present (dashed boxes), or newly created when polymerases add nucleotides in template-independent manner—is often used to guide end joining. The process is error-prone and can result in diverse DNA sequences at the repair junction (bottom). Although NHEJ is also less commonly capable of joining 2 DNA ends without nucleotide loss from either DNA end and without any addition, ends of radiation-induced DSBs are not amenable to direct ligation but rather require end-processing by nucleases or polymerases. Nucleotide additions are depicted in green lowercase. (Adapted with permission of (13).)

TABLE 1

Form of the Dose–Response for Radiation Tumorigenesis (2)

Step	Description^*
1	Increasing exposure leads to linear increase in number of electron tracks, which increases probability of biologic effect (2).
2	DNA DSBs are most concerning biologic effect (2,7,9–11).
3	Cellular response to DSBs often leads to cells that survive the damage but contain DNA mutations (2,5–7,8,12,16).
4	DNA mutations lead to cancer initiation and progression in humans (2,6).