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Free radicals, the chemical, not the political kind, are dangerous to cells. Produced by such diverse forces as ultraviolet radiation, X rays, and food burned on a barbecue, a hydroxyl radical, a duo of oxygen and hydrogen atoms (HO) that was once part of a water molecule (H2O), can seriously damage DNA. The damage can take several forms -- for instance, the radical can attach to one of the bases (adenine, thymine, guanine, or cytosine) that are strung together to make up the sides of the ladder-like DNA scaffold and form a bulge, or it can break one or both sides of the ladder. In most cases, damage is detected by repair proteins, setting in motion a complex repair process.
Tom Tullius, a chemistry professor and chairman of the chemistry department, is interested in how DNA repair is initiated. In particular, he has focused on how a single strand break -- a single missing base and sugar on one of the two strands -- is detected. Recently, Tullius and Hong Guo, a former student of his from Johns Hopkins, who is now at Protometrix, Inc., in Guilford, Conn., have taken a significant step toward understanding this process.
They created DNA molecules bent at a specific location to provide a fixed reference point against which they could understand changes in the structure of the molecule. They then exposed the DNA to hydroxyl radicals to create a library of molecules with gaps at different places along one of the strands. They used a two-dimensional gel electrophoresis system to reveal the resulting shapes. Tullius and Guo found that a second bend was created at the site of the break, and that it was stable and bent in a specific direction relative to the reference bend. The researchers hypothesize that the bend at the site of the break may be the signal by which the cellular repair proteins recognize the problem.
This work was reported in the April 1, 2003 issue of the Proceedings of the National Academy of Science. |
