Our cells perform a marvel of engineering when it comes to packing information into small spaces. Every time a cell divides, it bundles up an amazing 4 metres of DNA into 46 tiny packages, each of which is only several millionths of a metre in length. Researchers from EMBL Heidelberg and the Julius-Maximilians-Universit\u00e4t W\u00fcrzburg have now discovered how a family of DNA motor proteins succeeds in packaging loosely arranged strands of DNA into compact individual chromosomes during cell division.<\/p>\n\n\n\n
The researchers studied condensin, a protein complex critical to the process of chromosome formation. Although this complex was discovered more than three decades ago, its mode of action remained largely unexplored. In 2018, researchers from the H\u00e4ring group at EMBL Heidelberg and their collaborators showed that condensin molecules create loops of DNA, which may explain how chromosomes are formed. However, the inner workings by which the protein complex achieves this feat remained unknown.<\/p>\n\n\n\n
\u201cWe have been working on this problem for a long time. But only now, by combining different experimental approaches, we have found an answer to this long-standing question,\u201d said Christian H\u00e4ring, former Group Leader at EMBL Heidelberg<\/a> and now Professor at the Julius-Maximilians-Universit\u00e4t W\u00fcrzburg<\/a>.<\/p>\n\n\n\n Through meticulously designed experiments, some of which involved observing and manipulating single condensin molecules while <\/em>they were in the process of forming DNA loops, the researchers found how different parts of the complex collectively act as a molecular machine: one part holds the DNA steady, like an anchor, whereas the other acts as a motor which moves the DNA forward, thus creating a wide loop.<\/p>\n\n\n\n Like other motor proteins, condensin takes \u2018steps\u2019 along the DNA, burning cellular energy in the form of ATP while doing so. However, these steps are more than 500 times longer than the steps taken by other DNA motor proteins, even though the amount of energy used is roughly the same. \u201cIt\u2019s like a formula one racing car with the energy efficiency of an e-bike,\u201d said Indra Shaltiel, the first author.<\/p>\n\n\n\n \u201cAdvancements in cryo-electron microscopy techniques allowed us to visualise this complex mechanism in unprecedented detail,\u201d said Sebastian Eustermann, Group Leader at EMBL Heidelberg<\/a> and a senior author of the study published in Science<\/em><\/a>. \u201cWe could capture condensin in action and derived a molecular choreography of how ATP fuels its motor activity \u2013 a key step towards understanding DNA loop formation. Similar loops and related molecular machines have been implicated in diverse genomic processes, including the control of how genes are switched on and off in between cell divisions. Consequently, our findings may have even wider implications.\u201d<\/p>\n\n\n\n Condensins belong to one of the most evolutionarily ancient families of chromosomal proteins. The discovery of this new mechanism thus opens up a whole new field of study. \u201cMembers of the class of motor proteins condensin belongs to are presumably essential for all life on earth,\u201d H\u00e4ring said. \u201cIt is obvious we are only just starting to understand their roles and how they might be affected in human conditions.\u201d<\/p>\n\n\n