Prof. Cees Dekker reveals DNA mystery

Prof. Cees Dekker’s team resolved a biological mystery in collaboration with foreign researchers from EMBL Heidelberg and Columbia University: how our genes are packed in cells. It was already known that DNA molecules, that have a size of two meters in each cells when they are stretched out, must be packed in some way. In 1882 it was already observed through a microscope how DNA molecules are packed into very small chromosomes prior to cell division. The question remained how these molecules are packed exactly.

It was already known that condensin plays a key-role in compacting chromosomes. Until recently, there were two theories on how condensin packages these molecules. One theory states that condensing works like a hook that can grasp somewhere in the jumble of DNA, thus tying it together. The other, more elegant theory, states that DNA is pulled as a loop through the ring shaped condensin. This more elegant theory theory, named loop extursion, seems to be the right one.

The greatest objection for this theory was that the process would cost more energy than was measured in the cells. The scientists discovered, however, that condensin has a motor function. The protein makes relatively large steps over the DNA molecule, which made the energy comsumption more in-line with the measurements. This process is observed and filmed in the Dekker lab by Postdoc Dr. Mahipal Ganji. He did this by fixing a DNA molecule on both ends on a glass surface in a microfluidic channel. On this record, it is clearly visible how the DNA gets more concentrated on a single spot, supporting the loop extursion theory to be the right one.  Surprising results are that the DNA is pulled asymmetrically through the condensin and that the process is slower when the DNA is under tension.

Not only does this settle a long-standing debate in biology, it also opens windows for further research. Problems with the protein family to which condensin belongs are related to inheritable diseases, for example Cornelia de Lange Syndrome (CdIS). Children with CdIS are almost always mentally disordered. Furthermore, condensin plays a crucial role in the organisation of chromosomes during cell division. Mistakes in this process could result in cancer. The scientific breakthrough can possibly help in the battle against these diseases.



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