Scientists’ understanding of how long strings of DNA are packaged into tiny spaces just got a little more complicated. New research on single molecules of DNA show that supercoils—segments of extra-twisted loops of DNA—can moving by “jumping” along a DNA strand. The results, published today (September 13) in Science, give researchers new insights into DNA organization and point to a surprisingly speedy mechanism of gene regulation inside cells.
“This is the first study that addresses the dynamics of DNA supercoils,” said Ralf Seidel, who studies movement of molecular motor proteins along DNA at the University of Technology Dresden, but was not involved in the research. This supercoil hopping motion “allows DNA strands to transmit supercoiling, bringing sites together in very fast manner.”
DNA, being a double helix, is naturally twisted. In vivo, it’s packaged with proteins called histones that help condense the millions or billions of nucleotides into the small space of a cell’s nucleus. Constant interaction with proteins moving along the strand, like transcription factors that need to open the helix to read the DNA sequence, can affect both the double helix’s twist, and the strand’s “writhe”—the coiling of the strand around itself. These extra-twisted coils, called plectonemes or supercoils, form not unlike coils in phone cords. By bringing together distant segments of DNA, such as regulatory elements and the genes they control, supercoiling can affect expression.
In order to get a better sense of how supercoils behave, Cees Dekker at Delft University of Technology and his colleagues induced supercoils in single strands of DNA molecules, labeled with fluorescent dye. One end of the DNA was anchored to the side of a glass capillary tube and a magnetic bead was attached to the other end. This allowed the researchers to use miniscule magnets to twist the DNA and induce supercoils, and watch their movement using fluorescence microscopy.
Unexpectedly, the team found that supercoils move along DNA strands in one of two ways. Sometimes they slowly diffuse along the strand; other times, the supercoils “hopped”—disappearing suddenly from one location while simultaneously appearing at a distant location further down the strand.
“This is far more complicated” than diffusion of supercoils down the DNA’s length, said Prashant Purohit, who studies DNA behavior at the University of Pennsylvania, but was not involved in the study. The DNA is behaving non-locally, he noted. “It shows that writhe”—the coiling of the DNA strand—“is a global, not local quantity [of the strand].”
So far the intriguing phenomenon has only been observed on single strands of naked DNA, Seidel cautioned, so it’s unclear how supercoils might act in vivo, when the DNA is well-packaged and studded with proteins. It may be that such behavior is more important for DNA in prokaryotic cells, which have less packaged DNA than eukaryotic cells, noted Bryan Daniels, who models biological systems at the Wisconsin Institutes for Discovery at the University of Wisconsin-Madison.
The ionic environment of the cell is also likely to influence supercoiling behavior. DNA is more likely to condense in the presence of multivalent ions (3 or more positive charges), for example, than in an environment of singly-valent ions. And Dekker and his colleagues, who used singly-valent ions in their experiments, found that more supercoils formed at lower concentrations of ions.
Dekker and his team are now looking at how different DNA sequences and the presence of DNA-binding proteins can influence supercoil formation and motion—the first step toward understanding supercoil movement in vivo.
“It’s amazing—60 years after the double helix, we’re still discovering the basic properties of DNA,” said Dekker.
M. T. J. van Loenhout et al., “Dynamics of DNA supercoils,” Science, doi: 10.1126/science.1225810, 2012.
Video by Marijn van Loenhout, courtesy Cees Dekker lab TU Delft