Salts add tightness to DNA supercoils.

Within the watery world of living cells, DNA molecules do a tortuous dance. First the chainlike strands wind themselves into helices. Then they bend and twist again, folding into gnarled supercoils.

At first glance, each strand resembles a tangled braid. In fact, the DNA supercoil is a carefully articulated knot that ties itself up according to rules governing its geometry and electrical forces acting on it from the liquid surroundings.

To understand more completely how DNA supercoils and the forces that make the strands writhe, Tamar Schlick, a mathematician and Howard Hughes Medical Institute researcher at New York University, and her colleagues have developed a computer model that links knot theory to biochemistry

Addressing a meeting of the Society of Industrial and Applied Mathematics in San Diego last week, Schlick explained that her computer simulations reveal the influence of salt concentrations on the tightness of DNA's supercoils.

Because dissolved salts carry an electrical charge, they can alter the shape of certain molecules with which they come in contact. Such behavior shows up clearly in the computer simulation, Schlick says.

While biochemists have known for some time that salts cause DNA's coils to tighten and loosen, they have lacked a comprehensive theory to explain how and why this happens.

Using a detailed computer model, says Schlick, her group has demonstrated clear differences in DNA shape and behavior depending on the amount of salt in a simulated molecule's environment. The team also posits a mechanism for these changes.

Examining how simulated DNA strands, each with 1,000 base pairs, interact with charged salt molecules at varying concentrations, the researchers found that the energies, shape, and motion of supercoiled DNA all "change dramatically as a function of salt." The DNA's form became "highly compact, bent, rigid, and interwound" as the amount of nearby salts rose, while in the presence of lesser amounts, the coils became "open, loose, and flowing in shape."

Moreover, the researchers found that the amount of salts surrounding DNA strongly affects the "buckling transition," in which a loop of DNA twists into a figure eight. Indeed, Schlick noticed that by raising the amount of salt, pieces of the loop would "slither" past one another and then undergo a "collapse," crunching up into a highly compressed form.

"These observations suggest a potential regulatory role for salts on DNA processes," Schlick says. In the presence of a solution rich in salts, the tightly coiled molecule "brings into contact segments of DNA that are far away in the linear sequence." These actions, she believes, could "potentially play important regulatory roles in [gene] transcription and recombination."

The behavior of DNA in the computer model, adds Schlick, shows a striking similarity to results culled from recent electron microscopy studies and laboratory experiments. Yet "the structural information that can be extracted from the simulations is far richer in detail than that offered by low-resolution measurements" in a laboratory she asserts.