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Arthur T Knackerbracket has found the following story:

New insights into the process of DNA-looping change our view of how the genome is organised within cells. The discoveries by IMP-researchers elucidate a fundamental mechanism of life and settle a decade long scientific dispute.

To pack the genetic information, inscribed in roughly two metres of DNA, into its nucleus, a human cell must achieve the equivalent of fitting an 80-kilometre-long thread into a sphere the size of a soccer ball. Looking through his microscope back in 1882, German biologist Walther Flemming already glimpsed at how this trick is done. What he saw were loops of DNA-strands inside the nucleus of an egg-cell that reminded him of the brushes that were used at the time to clean gas lanterns - and so he named these structures lampbrush chromosomes, without an idea of what they were and which purpose they served.

It took many decades to identify the lampbrush chromosomes as strands of DNA neatly folded into loops, even longer to realise that DNA is folded into such structures in all cells and at all times, and it took until now to find out how this folding is done. In a paper published by the journal Science, researchers from Jan-Michael Peters’ lab at the Institute of Molecular Pathology (IMP) in Vienna demonstrate for the first time that a molecular machine actively and purposefully folds DNA via “loop extrusion” and thereby fulfils several important functions in the interphase cell.

That the process of looping DNA is neither random nor arbitrary is evident from how evolutionary ancient it is. All organisms do it, from bacteria to humans. The primeval function of the folding mechanism is still unknown and we may never find out, but some vital tasks have been discovered in recent years. By looping DNA, distant regions on the large molecule are brought into close proximity and are able to interact. This physical contact plays an important role in gene regulation, where DNA segments called enhancers influence which genes are active. Looping is also essential for the ability of immune cells to produce a diverse array of antibodies.

[...] The team involving Davidson, a senior postdoc in the Peters-lab at the IMP, was able to reconstitute cohesin function in a simplified system in vitro. Thus, he could watch how single cohesin molecules rapidly extruded single pieces of DNA into loops, exactly as Mirny and others had postulated. His findings, published online on 21 November 2019, are far reaching and change the way we perceive our genome in several different aspects:

• Rather than being static, the genome is a highly dynamic structure.
• The folding of genomic DNA is an actively regulated process. It involves looping the DNA molecule by way of extrusion, with many loops being constantly in motion.
• The looping process is mediated by cohesin which must therefore be a molecular motor, similar to other motor proteins such as myosin which makes our muscles move.
• The cohesin molecule does not just form carabiner-like rings around DNA but must attach to DNA dynamically via several binding sites to be able to fold it. This must also be true for a related molecule, condensin, as has been shown last year.

“This is a real paradigm shift”, says IMP director Jan-Michael Peters. “Earlier observations already gave us some hints, but the work of Iain Davidson is now proof. In my scientific life, few other discoveries were as far-reaching as this one.”

The paper “DNA loop extrusion by human cohesin” by I.F. Davidson et al. was published online by the journal Science on Thursday, 21 November, 2019.

Original Submission