In fact, if we put all the DNA chains contained in all the cells of the human body end to end, we would have enough to go back and forth between the Earth and the Sun… more than 300 times!
It is obvious that, to accommodate in the cell nucleus, the DNA must be folded on itself many, many times. But what is less obvious is how the cellular machinery can still have access to all these genes — which is essential for making proteins and repairing the damage that DNA endures daily — if the genome is at this point folded back on itself. And this is precisely what a team from Laval University and UCLA – Berkeley managed to understand in a study published in August.
“It is a complex of molecules which is essential to life, essential to development, but which is reduced in certain neurodegenerative diseases and which becomes oncogenic [cause de cancer] when he is transferred, says Jacques Côté, researcher at UL and one of the main authors of the article. One of the advantages of finally knowing its structure in high definition is that it could possibly give us new therapeutic targets.”
At the molecular level, DNA needs named proteins histones to fall back. He does this the first time to form small “balls”, the nucleosomes, which are attached one after the other and which roll up on themselves to form a sort of “roller”. Then, these fold and roll up several more times in turn until they become very compact packages – the famous chromosomes.
In total, says Mr. Côté, there are 17 different proteins that play roles in this, a complex called TIP60.
“Nowadays, we usually use artificial intelligence tools to predict how a protein will fold on itself, but in an assembly of 17 proteins, this is simply impossible.”
— Jacques Côté, researcher at Laval University
Like a photo
The authors of the study therefore did not “calculate” the behavior of the complex, but took pictures of it, so to speak. UL researchers have in fact isolated and purified the TIP60 complex in a human cell and sent it to Berkeley, whose labs are equipped to carry out “electron cryomicroscopy”.
This is a technique which consists of freezing an organic molecule and bombarding it with electrons, which makes it possible to produce a 3D image with extraordinarily precise resolution – the technique has also won the Nobel Prize in Chemistry in 2017.
The researchers were thus able to map the protein complex with a resolution of 0.5 nanometers (nm, 1 nm = 1 millionth of a millimeter). We can get an idea of the precision this represents by knowing that a strand of DNA is approximately 2 nm wide, nucleosomes 11 nm in diameter and chromosomes approximately 1400 nm thick.
This therefore made it possible to probe the structure of the TIP60 complex in great detail. “And then, based on that, we [au Centre de recherche du CHU de Québec] tested a series of modifications to confirm the structure and understand how this protein complex is capable of providing access to different genes,” explains Mr. Côté.
This work appeared in the prestigious journal Sciencewhich gives an idea of their importance.
How the cell manages to access its genes through histones and all the folds of DNA is in fact a fundamental element of its functioning. Genes are “protein recipes”: their role is to store the information necessary for assembling the tens of thousands of different proteins that the body produces.
If a mutation in one of the 17 TIP60 proteins impairs access to a tumor suppressor gene, for example, then that protein will be less expressed and the risk of cancer will increase. And there are plenty of other diseases that can be caused or aggravated by the expression (too low or too high) of genes, which is partly regulated by TIP60. Solving its structure and functioning could therefore potentially lead to numerous medical applications.
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The year 2024 was rich in discoveries for the capital's scientific community. Each in their own field, researchers from the region have written new chapters in scientific history. The Sun presents to you, one per day, the most significant breakthroughs of the year.
– Dec 23 : Hormone party (with surprise guest)
– Dec. 24 : The DNA packager
– Dec 25 : Glacier «on the rocks»
– Dec 26 : Soon “organic” electrodes?
– Dec 27 : The family will wait…
