Knotted DNA Can Lead to Cell Death

June 6, 2007

The three or more feet of DNA within any cell twists, coils, and compacts itself to fit snugly within a cell's nucleus. These slender strands also have to unpack themselves for replication to occur. Sometimes, knots form during the intricate packing and unpacking that takes place. Now, researchers have a better sense of the cellular consequences of DNA knots.

Microbiologist Lynn Zechiedrich of the Baylor College of Medicine, mathematician Jennifer K. Mann of Florida State University, and their colleagues report that DNA knotting causes the loss of genetic material, which leads to gene malfunctions and cellular death. Their report appears in the current issue of the online journal BMC Molecular Biology.

The researchers investigated the effects of tight knotting on the DNA of Escherichia coli, a common bacterium. They found that DNA replication and the transcription of genes to active proteins within the bacteria are stymied by knotting. Unknotting enzymes called topoisomerases, furthermore, are often unable to unravel the tangles quickly enough to prevent toxic events that lead to cell death.

Topoisomerases perform crucial unknotting functions in not only bacterial but also human cells. And they can be important anti-cancer drug targets. "Understanding what these enzymes do in a cell," Zechiedrich said, "may help us better understand how these drugs stop infections and cancer."

Source: Baylor College of Medicine, May 29, 2007