For the first time, it was observed in real time that condensed protein extruded DNA to form a circular structure

What's striking is that living cells, when they're ready to divide, can pack a jumble of DNA up to two meters long into tiny, neat chromosomes However, scientists have been puzzled for decades about how this process happened Now, in a new study, researchers from the kavley Institute at Delft University of technology in the Netherlands and the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, have isolated the process, photographed it, and observed in real time how a protein complex called condensin wraps DNA to squeeze out a loop 。 By squeezing out many of these circular structures in the long DNA chain, the cell effectively compresses its genome, so that the genome in the cell can be evenly distributed to its two daughter cells The relevant research results were published online in the journal Science on February 22, 2018, with the title of "real time imaging of DNA loop extension by condensation"   This discovery has solved a heated debate in this field, because it has finally solved the problem in biology that has been discussed for more than a century: before two daughter cells are produced, the DNA in cells is like spaghetti -- DNA strands mixed together The cell needs to assemble these impurities in the chromosome to be able to distribute its DNA neatly into two daughter cells For many years, it has been clear that as a protein complex, condensation protein plays a key role, but before that, biologists had different opinions on how condensation protein works One theory is that condensation proteins act like a hook that can grab the DNA in this DNA mess and connect it together Another theory is that a ring-shaped condensation protein pulls DNA inward, allowing it to form a ring structure In a cover paper published in the journal Science in November last year, scientists from research institutions such as Delft University of technology confirmed that condensation protein has the motor function needed to squeeze out the ring structure (Science, DOI: 10.1126 / science Aan6516) This adds an important new content to the puzzle, but as Kim Nasmyth of Oxford University published a viewpoint type paper (Science, As pointed out in doi: 10.1126/science.aap8729, "condensation protein is a kind of DNA transposase discovered, of course, as a kind of loop extruder The idea of "extruder" is the same, but this does not mean that it confirms this point The challenge is still to observe extrusion and transposition, so as to determine whether it is a monomer or a polymer complex, and clarify its molecular mechanism " Now that has been confirmed Together with Christian haering of the European Molecular Biology Laboratory in Heidelberg, Germany, the Cees Dekker team at the kavley Institute at the University of Delft has produced images of this condensed protein complex as it works - squeezing out the circular structure of DNA The haering team developed purification methods and fluorescent labeling methods for this protein complex Mahipal Ganji, a postdoctoral researcher at Dekker Laboratory of the kavley Institute at the University of Delft, said, "we only confirm this by taking images DNA is such a jumble that it's hard to isolate and study the process in cells In our study, the first step is to fix two ends of DNA molecule on one surface, and mark DNA and condensation protein with color dye Then by adding a liquid in a direction perpendicular to the DNA molecule and letting it flow, we make the DNA U-shaped and place it on the focal plane of our microscope Surprisingly, we were then able to see a single protein binding and extruding a ring structure " Dekker added, "this settled the dispute These data provide convincing evidence that condensation proteins bind to DNA to form a circular structure Our new imaging method also allows us to measure various types of quantitative data: the symmetry of ring extrusion, the speed of ring formation and what happens when DNA is pulled " The researchers found that the rate of formation of this ring structure is very high: condensation proteins can wrap up to 1500 base pairs in DNA per second And it only consumes an appropriate amount of cell fuel ATP to do so, which shows that the condensation protein does not move along the DNA base by base, but pulls it with great strides When DNA is pulled slightly, the formation of the ring slows down Obviously, in the presence of tension, the condensation protein seems to work harder to squeeze the DNA, resulting in a circular structure Surprisingly, the ring squeeze was asymmetric: "we observed that the condensation protein anchored to the DNA and anchored itself there, and then it began wrapping the DNA only from one side." "So far, this is another interesting finding," Dekker added This study represents an important step in the basic understanding of DNA and also has an important impact on medicine Errors in the SMC protein family to which condensation proteins belong are associated with hereditary diseases such as Cornelia de Lange syndrome Condensation proteins also play a crucial role in the assembly of chromosomes during cell division, and errors in this process can lead to cancer A better understanding of these processes is essential for tracking the molecular origins of serious diseases.