Folding Away Meters of DNA With Flexible Mini-Clamps

Originally published by TU Delft

February 18, 2016

DNA molecules are like extremely long strands of fairy lights: it's almost impossible to disentangle them and store them neatly. A single cell contains two metres of DNA molecules, but is somehow able to fold them neatly into chromosomes measuring just a few micrometres. The protein condensin is known to play a key role, but the details of the process are still largely a mystery. For the first time ever, researchers from TU Delft's Kavli Institute of Nanoscience and the European Molecular Biology Laboratory in Heidelberg have successfully filmed the behaviour of an individual condensin molecule. They discovered that the protein is actually a lot more dynamic than was previously thought. They published an article on the subject on February 18 in the online version of the journal Cell Reports. The article is selected as the cover article for the March 1 issue. A better understanding of how condensin works may provide more insight into the development of a group of diseases in which malfunctions in condensin seem to play a role. The condition microcephaly, which is currently being linked to the Zika virus, is an example.

Dynamic Molecule

“Until now, condensin was generally seen as a somewhat stiff molecule. To try to explain it, you can compare it with a hair clip: condensin secured the DNA in loops by clicking open and closed. But our latest research shows that it would be better to compare it with an elastic band,” says Jorine Eeftens, doctoral candidate in Cees Dekker's research group. “We witnessed condensin as an extremely dynamic molecule, darting back and forth before our eyes under the microscope. We also discovered that condensin has four different positions rather than two: not just open (V) and closed (O), but also a sort of double loop (B) and a semi-open position (P). Condensin probably uses these different positions to attach to the DNA before storing it away compactly. We are now conducting further experiments to find out exactly how this works.”

Cell division

The protein condensin is essential to all living cells: the proteins act as ‘clamps’, allowing cells to fold strands of DNA neatly into compact chromosomes. During cell division, it is crucial that DNA divides itself equally between the daughter cells so that both have the DNA material from the start. Cells do this by splitting the X-shaped chromosome at the crossover point and sharing the halves between the daughters.

Zika virus

Although most of the research is focused on gathering fundamental information about cell division, it could also be important in terms of helping to understand how certain diseases develop. The condition microcephaly, whereby children are born with an abnormally small skull, is an example. Several causes of microcephaly have already been identified; the effect of condensin may prove to play a role in the genetic cause. Cases of microcephaly in South America are currently being linked to the Zika virus.