UIC RESEARCHER UNTANGLES MYSTERY OF KNOTTED DNA

When the double helix strands of DNA collide and tangle inside the nucleus of a cell, the result can be deadly. Now, as reported in the Oct. 28 issue of the journal Nature, researchers at the University of Illinois at Chicago have proposed an explanation of how DNA is disentangled-a secret that may someday aid in developing new treatment methods for deadly diseases, like E. coli bacterial infections and even some forms of cancer.

John Marko, a UIC physicist, who collaborated with Jie Yan of UIC and Marcelo Magnasco at the Center for Studies in Physics and Biology at Rockefeller University, says that the unbelievably long and snarled DNA strands of the cell are disentangled by enzymes called topoisomerases. Several years ago, scientists discovered that topoisomerases disentangled DNA not by random collisions, as had been thought, but through the topoisomerases actually detecting the complex topology of a DNA strand. Yan, Marko and Magnasco have proposed a mechanism explaining how the enzymes can figure out the twists and turns of DNA strands. Discovering how topoisomerases work may be a key to developing antibiotics to fight bacterial infections, and in developing chemotherapy treatments that kill only cancerous cells.

"The question is, can you kill tumor cells, or the bacteria in an infection, before killing the person?" Marko says hypothetically. "With survival of the fittest, you have bacteria growing today that are stronger than the antibiotics made to combat them."

Understanding topoisomerases, then, will enable scientists to better understand cell division, which in turn can be used to counteract an infection's bacterial chain of events. Though there are some antibiotics being developed today that interfere with unhealthy topoisomerases, Marko says, there are many problems with these drugs. "The idea is that you eventually want to be able to target the topoisomerases in the cells that you want to kill," Marko says. "Then you can shut only those topoisomerases down."

While in the nebulous world of science, the direct applications are still down the road, Marko's theoretical research might prove to be a key component of fighting even the heartiest of bacteria. "It's a very speculative theory at this point, but it will spark new experiments," Marko says. "The point of studying topoisomerases is that if you can mess with them, you can successfully manipulate a cell's behavior."

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