7th Jan 2020

Why is it good to keep DNA in the loop?

7th Jan 2020

Curated by Roman Barth

This could be vital in medicine, like cancer therapy and also in understanding how our cells multiply: researchers have identified a mechanism by which long DNA molecules pack themselves into the tiny space inside a cell.

In 10 seconds? Scientists have untangled a mystery – how DNA forms loops in the nucleus of our cells to avoid being tangled and becoming useless. The process also plays a role in transcribing genetic code into proteins which can occasionally malfunction, leading to diseases. (Read the science)

DNA loops

Loops? And then what? Let’s start with a fun fact: the human DNA is 2-3m long and it is present in every cell. But cells are only a few micrometres in diameter. So, DNA needs to be folded up to fit in. On top of that, every now and then, important parts need to be 'pulled out', so that proteins can be produced – these are vital for various functions our cells want to perform. (More on DNA loops).

But doesn’t this pulling create a mess? Well, good question! If DNA would be like an unordered globule of yarn, it would be like the box at home with all those forgotten and entangled cables. Remember, what a nightmare it is to find the one you're looking for? The same would happen to our DNA that contains the code of life. It would not be able to move anymore, which would be lethal to our cells as the necessary code fragments would not be accessible to be copied. (Find out more) 

So, how come DNA loops don’t get entangled? Hail a newly discovered amazing mechanism, that neatly folds up the ‘molecule of life’. What is even more amazing, is that it constantly moves and pulls the loops so, distant code fragments can be joined to create specific proteins and new antibodies that fight certain diseases. (More on this here)

Wow, and what’s the engine behind it? A series of new studies identified a protein, called cohesin that drives the so-called loop extrusion process. It is a large, ring-shaped molecule that is likened to a carabiner because it can grab DNA. It can slide along and stop to pull when it encounters a molecular barrier, like a knot on a rope. Different loops are pulled out to combine the genetic code fragments they carry. (Read more)

You describe it as if it was visible… Well, yes! In 2018, for the very first time, researchers directly observed that condensin, (which belongs to the same family of proteins as the cohesin mentioned above), found in yeast can make DNA loops (admire the beautiful images and videos here). Now, after more than one and a half years, this process was shown to work for other proteins of the condensin-family from a frog species and, importantly, humans. My team used state-of-the-art optical microscopy and machine learning to directly visualize the distribution of DNA in the cell nucleus at the nanoscale. We simultaneously monitored the motion of DNA to which those proteins contribute for the first time! (Read more here)

And where do we go from here? Well, for many people this discovery will be useful when translated into a medical application. But the next quest is to establish if this mechanism is also the same in bacteria and in other organisms. Then, we must find out how the DNA loops and the looping proteins interact with other processes in the cell. For example, can they influence how often a certain gene is transcribed? There is also much work to be done to translate these findings from the nanoscale to whole organisms – how can we tackle diseases caused by the malfunctioning of these DNA-looping proteins? So, stay tuned! (More on DNA-looping in bacteria)

Untangling the yarn of genome biology

The field experienced a great boost about 20 years ago with a novel technology allowing to map which piece along the DNA frequently interacts with others.

This revealed that some regions that are distant along the genome, contact each other more often than expected in three-dimensional space. Compartments, sub-compartments, sub-sub-compartments were seen. 

Our DNA is thus very well organized, nothing like your cable tangle. 

Earlier research using computer simulations originating from these experiments already suggested that DNA was organized into loops, but the recent discovery now finally confirmed this notion and also reveals the complex process by which loops are formed.

The molecule can actively pull out DNA sections and form loops on the go allowing for the mixing of genetic code when creating new antibodies, for example.

(Psst, Roman distilled 29 research papers to save you 2725.7 min)