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New Method Offers Insight Into Radiation Damage to DNA

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DNA-Monitoring Method Wins Pollution Prevention Award

The new technique of using fluorescently labeled molecules earned biologists Betsy Sutherland and Brigitte Paap a “Best in Class” pollution prevention award from the U.S. Department of Energy’s (DOE) Office of Science. This technique may now be used throughout the DOE labs and in universities and industry. More...

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 down stream, 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,” Sutherland said.

Since many enzymes participate in the repair of DNA, the Brookhaven investigators now plan to study the effectiveness of these enzymes in repairing the complex damages modeled by the technique using dual-color fluorescent tags.