Release date: 2018-02-26
What's striking is that when living cells are ready to split, they can pack a bunch of messy up to two meters of DNA into neat tiny chromosomes. However, scientists have been confused for how this process has happened for decades. Now, in a new study, researchers from the Kavli Institute of Delft University of Technology in the Netherlands and the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, separated the process and filmed it. And real-time observation of how a protein complex called condensin wraps around DNA to squeeze out a loop. By extruding many such circular structures in the long chain of DNA, the cell efficiently compresses its genome, so that the genome in the cell can be evenly distributed into its two daughter cells. The relevant research results were published online in the journal Science on February 22, 2018, and the title of the paper is "Real-time imaging of DNA loop extrusion by condensin".
This discovery solves a heated debate in this field because it ultimately answers the question that has been discussed in biology for more than a century: before the production of two daughter cells, the DNA in the cell is like a spaghetti - - DNA strands are mixed together in a mixed manner. Cells need to assemble these hybrids in the chromosome so that their DNA can be neatly distributed into two daughter cells. For many years, it has been established that condensed proteins play a key role as a protein complex, but before that, biologists had differences about how condensed proteins work. There is a theory that condensed proteins act like a hook that captures the DNA in this DNA hybrid and joins it together. Another theory is that a circular condensing protein pulls DNA inward, allowing it to form a ring structure.
In a cover paper published in the journal Science last November, scientists from research institutes such as Delft University of Technology confirmed that condensed proteins have the motor function required to squeeze out such a ring structure (Science , doi:10.1126/science.aan6516). This adds an important new dimension to this puzzle, but as pointed out by Kim Nasmyth of the University of Oxford in the same period in Science (Doci:10.1126/science.aap8729), The discovery that a protein is a DNA translocase is of course consistent with its idea of ​​functioning as a loop extruder, but this does not mean that it confirms this and faces The challenge remains to observe extrusion and translocation to determine whether it is a monomer or a multimeric complex and to elucidate its molecular mechanism."
This has now been confirmed. The Cees Dekker team at the Kavli Institute of Delft University, together with the Christian Haering team at the European Molecular Biology Laboratory in Heidelberg, Germany, photographed this condensed protein complex - it squeezed out the DNA loop Shaped structure---the image of time. The Haering team developed a purification method and a fluorescent labeling method for this protein complex.
Mahipal Ganji, a postdoctoral researcher at Dekker Lab at the University of Delft, Delft University, said, "We just confirmed this by taking images. DNA is so a messy mixture that it is difficult to separate this in cells. A process is studied. In our study, the first step is to immobilize the two ends of the DNA molecule on a surface and perform color dye labeling on the DNA and the condensed protein. Adding liquid in the vertical direction and letting it flow, we make this DNA appear U-shaped and place it on the focal plane of our microscope. Surprisingly, we can then observe a single condensin binding Go up and squeeze out a ring structure."
Dekker added, “This resolves the debate. These data provide compelling evidence that the condensed proteins will wrap around the DNA to form a ring structure. Our new imaging method also allows the measurement of various types of quantitative data. : the symmetry of the ring extrusion, the rate of formation of the ring structure and what happens when the DNA is pulled."
These researchers found that the rate of formation of this cyclic structure is very high: condensing proteins can entangle up to 1500 base pairs in DNA per second. Moreover, it only consumes an appropriate amount of cellular fuel ATP, which indicates that the condensed protein does not move along the DNA on a base-by-base basis, but rather pulls it over a large step. This ring structure formation process slows down when the DNA is pulled slightly. Obviously, in the presence of tension, the condensing protein appears to work harder to squeeze the DNA, resulting in a cyclic structure. Unexpectedly, this ring extrusion is asymmetrical: "We observed that the condensin docked on the DNA and anchored itself to it, then it began to wrap the DNA from only one side." Dekker added Tao, "This is another interesting discovery so far."
This research represents an important step in the basic understanding of DNA and has an important impact on medicine. Errors in the SMC protein family to which condensin belongs are associated with hereditary diseases such as Cornelia de Lange Syndrome. Condensed proteins also play a crucial role in chromosome assembly during cell division, and errors in this process can lead to cancer. A better understanding of these processes is critical to tracking the molecular origins of serious diseases.
Source: Bio Valley
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