This is How DNA Knots Could Help Improve Genome Sequencing Accuracy
Just like any long polymer chain, DNA tends to form knots.
Using technology that allows them to stretch DNA molecules and image the behaviour of these knots, MIT researchers have discovered, for the first time, the factors that determine whether a knot moves along the strand or “jams” in place.
“People who study polymer physics have suggested that knots might be able to jam, but there haven’t been good model systems to test it,” says Patrick Doyle, the Robert T. Haslam Professor of Chemical Engineering and the senior author of the study. “We showed the same knot could go from being jammed to being mobile along the same molecule. You change conditions and it suddenly stops, and then change them again and it suddenly moves.”
The findings, published in Physical Review Letters, could help researchers develop ways to untie DNA knots, which would help improve the accuracy of some genome sequencing technologies, or to promote knot formation. Inducing knot formation could enhance some types of sequencing by slowing down the DNA molecules’ passage through the system, the researchers say.
DNA knots also occur in living cells, but cells have specialized enzymes called topoisomerases that can untangle such knots. The MIT team’s findings suggest a possible way to remove knots from DNA outside of cells relatively easily by applying an electric field until the knots travel all the way to the end of the molecule.
This could be useful for a type of DNA sequencing known as nanochannel mapping, which involves stretching DNA along a narrow tube and measuring the distance between two genetic sequences. This technique is used to reveal large-scale genome changes such as gene duplication or genes moving from one chromosome to another, but knots in the DNA can make it harder to get accurate data.
For another type of DNA sequencing known as nanopore sequencing, it could be beneficial to induce knots in DNA because the knots make the molecules slow down as they travel through the sequencer. This could help researchers get more accurate sequence information.
Using this approach to remove knots from other types of polymers such as those used to make plastics could also be useful, because knots can weaken materials.
The researchers are now studying other phenomena related to knots, including the process of untying more complex knots than those they studied in this paper, as well as the interactions between two knots in a molecule.
Materials provided by Massachusetts Institute of Technology. Note: Content may be edited for style and length.