DNA molecules directly interact with each other based on sequence

Proteins play a large role in DNA regulation, but a new study finds that DNA molecules directly interact with one another in a way that's dependent on the sequence of the DNA and epigenetic factors. This could have implications for how DNA is organized in the cell and even how genes are regulated in different cell types, the researchers say.

"We are still only starting to explore the physical properties of DNA. It's not just a string of letters," Aksimentiev said. "It's a complex molecule with unique characteristics. The prevailing hypothesis is that everything that happens inside the nucleus, the way the DNA is organized, is all the work of proteins. What we show is that direct DNA-DNA interactions may play a role in large-scale chromosome organization as well."

Using the Blue Waters supercomputer at the National Center for Supercomputing Applications on the Illinois campus, Aksimentiev and postdoctoral researcher Jejoong Yoo performed detailed simulations of two DNA molecules interacting in a charged solution such as is found in the cell. The supercomputer allowed them to map each individual atom and its behavior, and to measure the forces between the molecules. They found that, though DNA molecules tend to repel each other in water, in a cell-like environment two DNA molecules can interact according to their respective sequences.

"In the DNA alphabet, there is A, T, G and C. We found that when a sequence is rich in A and T, there is a stronger attraction," Aksimentiev said. "Then we looked at what actually causes it at the molecular level. We like to think of DNA as a nice symmetrical helix, but actually there's a line of bumps which are methyl groups, which we find are the key to regulating this sequence-dependent attraction."