Simulations show how to unknot our genome
Topological entanglements severely interfere with important biological processes. For this reason, genomes must be kept unknotted and unlinked during most of a cell cycle. Computational evidence shows that structural-maintenance-of-chromosomes (SMC) proteins, such as cohesins and condensins, can cooperate with type II topoisomerase enzymes to establish a synergistic mechanism to resolve topological entanglements.
In each of our cells we have 2 meters of DNA stored and tightly packaged within a space that is about the width of a hair (10 µm or 0.00001 meters) (note that the thickness of DNA is about a thousand times thinner than a hair (2 nm or 0.000000002 meters).
Given such a huge length and such strong confinement, we would expect that our DNA would form complicated knots and links (a little bit like what you get when pulling headphones out of your pockets). The problem is that knots in DNA would impair vital biological processes such as gene transcription and cell division. Luckily for us, long-standing conjectures and recent evidence suggest that DNA is not heavily knotted at all.
While it is known that special proteins called topoisomerase can perform sophisticated 'topological" operations on DNA, no existing model has been able to explain how they maintain our DNA entanglement-free under the extremely confined and crowded conditions of the cell nucleus.
This latest research shows that a family of slip-link-like proteins called "Structural Maintenance of Chromosome" (SMC) can help topoisomerase to systematically resolve topological entanglements, even under physiological crowding and confinement. This slip-link protein is conjectured to act very much like a belay device for rock climbers: it links together two segments of DNA and can slide back and forth to enlarge or reduce the loop in between the linked segments. Through this action, knots or links that are caught in between the slip-link are squeezed and compressed until they are easily detectable and removable by topoisomerase, which would otherwise have a hard time to find them.
Given the ubiquity of topoisomerase and SMC proteins (which are found in virtually every life-form, from bacteria to humans), we argue that the mechanism that we uncovered in this work plays an important role throughout the cell cycle and across different organisms.