Shaping up the genome for cell division: Researchers have uncovered the internal workings of the molecular equipment that shapes chromosomes throughout cell division

Shaping up the genome for cell division: Researchers have uncovered the internal workings of the molecular equipment that shapes chromosomes throughout cell division

Our cells carry out a marvel of engineering on the subject of packing data into small areas. Each time a cell divides, it bundles up a tremendous four meters of DNA into 46 tiny packages, every of which is simply a number of millionths of a meter in size. Researchers from EMBL Heidelberg and the Julius-Maximilians-Universität Würzburg have now found how a household of DNA motor proteins succeeds in packaging loosely organized strands of DNA into compact particular person chromosomes throughout cell division.

The researchers studied condensin, a protein complicated crucial to the method of chromosome formation. Though this complicated was found greater than three a long time in the past, its mode of motion remained largely unexplored. In 2018, researchers from the Häring group at EMBL Heidelberg and their collaborators confirmed that condensin molecules create loops of DNA, which can clarify how chromosomes are fashioned. Nevertheless, the internal workings by which the protein complicated achieves this feat remained unknown.

“We now have been engaged on this downside for a very long time. However solely now, by combining completely different experimental approaches, now we have discovered a solution to this long-standing query,” stated Christian Häring, former Group Chief at EMBL Heidelberg and now Professor on the Julius-Maximilians-Universität Würzburg.

By means of meticulously designed experiments, a few of which concerned observing and manipulating single condensing molecules whereas they had been within the strategy of forming DNA loops, the researchers discovered how completely different components of the complicated collectively act as a molecular machine: one half holds the DNA regular, like an anchor, whereas the opposite acts as a motor which strikes the DNA ahead, thus creating a large loop.

Like different motor proteins, condensin takes ‘steps’ alongside the DNA, burning mobile power within the type of ATP whereas doing so. Nevertheless, these steps are greater than 500 instances longer than the steps taken by different DNA motor proteins, though the quantity of power used is roughly the identical. “It is like a method one racing automobile with the power effectivity of an e-bike,” stated Indra Shaltiel, the examine’s first writer.

“Developments in cryo-electron microscopy strategies allowed us to visualise this complicated mechanism in unprecedented element,” stated Sebastian Eustermann, Group Chief at EMBL Heidelberg and a senior writer of the examine revealed in Science. “We might seize condensin in motion and derived a molecular choreography of how ATP fuels its motor exercise — a key step in the direction of understanding DNA loop formation. Comparable loops and associated molecular machines are concerned in various genomic processes, together with the management of how genes are switched on and off in between cell divisions. Consequently, our findings could have even wider implications.”

Condensins belong to some of the evolutionarily historic households of chromosomal proteins. The invention of this new mechanism thus opens up an entire new area of examine.

“Members of the category of motor proteins condensin belongs to are presumably important for all life on earth,” Häring stated. “It’s apparent we’re solely simply beginning to perceive their roles and the way they could be affected in human situations.”

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