At the Brookhaven National Lab, scientists are helping to explain why ionizing radiation, from heavy, charged particles, is more damaging to the DNA structure than the non-ionizing variety of the type emitted from X-ray machines.
Using standard techniques of molecular biology, the scientists created synthetic DNA with known lesions in a variety of spatial arrangements with a red fluorescent tag attached to one end of the strand and a green fluorescent tag at the other end. They then applied a DNA repair enzyme, which clips the DNA at damaged sites. The scientists then used gel electrophoresis to separate the fragments according to their length. By looking at the red- and green-tagged bands, and determining their length, the scientists were able to measure how well the repair enzyme recognized and repaired the DNA damage.
The results were surprising: Instead of being dependent on the number of lesions, the ability of the repair enzyme to recognize the damaged sites appeared to be most affected by the spatial arrangement of lesions on the DNA strands. The scientists found that the enzyme readily recognized and repaired lesions on one of the DNA’s two strands that occurred all to one side of a reference lesion on the opposite strand (think of it as “upstream”). These upstream lesions were successfully repaired regardless of whether there were only two or many lesions in the damage. If the lesions occurred “downstream” from the reference lesion, however, the repair enzyme was unable to work properly, no matter whether the clustered damage was a simple, two-lesion cluster, similar to those caused by x-rays, or a complex multi-lesion cluster like those induced by space radiation. When the lesions occurred in a two-sided cluster both up and downstream from the reference lesion, again the repair enzyme worked poorly.
“Since x-rays produce about half upstream, easily repaired clusters and about half downstream, repair-resistant clusters, about half of them would be readily repaired,” Sutherland said. “The heavy, charged particles in space radiation, on the other hand, produce much more complex, two-sided clusters, containing so many lesions that most of them are repair-resistant. This directional dependence of the ability to repair lesions explains why damage from charged-particle radiation, such as that encountered in outer space, is more harmful,” she said.
Press release: New Method Offers Insight into Radiation Damage to DNA
Image caption: Sutherland’s team found that clustered DNA lesions that occur “upstream” of a reference lesion on the opposite DNA strand (blue marker) are repaired well (indicated by green), while lesions that occur “downstream” or to both sides of the reference lesion are repaired poorly (red). X-rays tend to produce equal numbers of up and downstream lesions, so about half the lesions are readily repaired. High-energy charged particles, on the other hand, produce much more complex two-sided clusters of lesions, making them harder to repair.
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