Loops, Flags and Tension in DNA
Published:18 May2023 Source:Delft University of Technology
Two protein complexes carry the major responsibility for the spatial organisation of chromosomes in our cell nuclei. DNA tension plays a surprising role in this. Together with Austrian colleagues, nanoscientist Cees Dekker and his PhD candidate Roman Barth of the Kavli Institute of Nanoscience at TU Delft now publish how they have visualised this in detail in Nature on April 19.
In 2018, Dekker and his group were the first to visualise how SMC protein complexes such as condensin and cohesin extrude loops in DNA. The DNA-binding protein CTCF was found to play a key role in the positioning of loops along the genome. DNA can be thought as a rope, onto which CTCF flags are pinned at two points, cohesin makes the loops from one flag to the other, but only if the CTCF is oriented correctly. Only one side of the CTCF protein is able to interact with cohesin. But it doesn't always do this.
Roman discovered that it made a difference whether the DNA strand was very loose or under tension. Without tension, cohesin often ignored the CTCF flag, even if correctly oriented, but when the DNA was under more tension, the CTCF acted as a perfect barrier. So, under the influence of DNA tension, CTCF becomes like a smart traffic light, allowing cohesin to pass or not, depending on the local traffic situation. When cohesin collides with a CTCF protein, it can stop or continue. It can also turn around, or even dissolve altogether.