DNA Repair More Efficient at Low versus High Doses of Ionizing Radiation

The Science

The biological effects of ionizing radiation are determined, in part, by the efficiency with which radiation damage is repaired as a function of dose. The standard model of radiation-induced cancer risk applies a linear relationship to extrapolate from high to low doses of ionizing radiation. Scientists at DOE’s Lawrence Berkeley National Laboratory, studying the formation of radiation-induced DNA repair-protein complexes, have shown that multiple DNA double-strand breaks produced 1 to 2 µm apart can rapidly cluster together to form damage repair centers. Surprisingly, they observed that the absolute number of repair centers is more than 4-fold smaller at high versus low doses of ionizing radiation. This new discovery supports the hypothesis that DNA damage repair is more efficient at low versus high doses of radiation and casts further doubt on current risk models, which assume that cancer risk from exposure to ionizing radiation is linearly proportional to dose in the low dose range.

The Impact

The standard model currently in use applies a linear scale, extrapolating cancer risk from high doses to low doses of ionizing radiation. However, the discovery of DSB clustering over such large distances casts considerable doubts on the general assumption that risk to ionizing radiation is proportional to dose, and instead provides a mechanism that could more accurately address risk dose dependency of ionizing radiation.

Principal Investigator

Sylvain V. Costes
Lawrence Berkeley National Laboratory

Co-Principal Investigator

Mina J. Bissell
Lawrence Berkeley National Laboratory

BER Program Manager

Resham Kulkarni

U.S. Department of Energy, Biological and Environmental Research (SC-33)
Biological Systems Science Division
[email protected]

References

Neumaier, T., J. Swenson, C. Pham, A. Polyzos, A. T. Lo, P. Yang, J. Dyball, A. Asaithamby, D. J. Chen, M. J. Bissell, S. Thalhammer, and S. V. Costes. 2012. “Evidence for Formation of DNA Repair Centers and Dose-Response Nonlinearity in Human Cells,” Proceedings of the National Academy of Sciences (USA) 109(2), 443-48. DOI: 10.1073/pnas.1117849108.