🧬 ALS, dementia, and cancer: a common origin discovered by researchers

Errors can appear when DNA copies itself, somewhat like mistakes in a transcribed text. Fortunately, a correction system is constantly on guard. But this mechanism isn't foolproof.

A study published in the journal Nucleic Acids Research reveals that a protein, until now known for its role in certain neurological diseases, can disrupt this balance. When a cell duplicates its DNA, small errors can slip into the sequence. To prevent them from accumulating, a system called "mismatch repair" acts like an automatic spell-checker. It spots the mistakes and corrects them quickly to preserve the genome's integrity.


The researchers focused on a protein named TDP43. It's already known for its involvement in certain diseases like amyotrophic lateral sclerosis (ALS) or some forms of dementia. Their goal was to understand its role in managing DNA errors.

Their results show that TDP43 acts as a regulator. It controls the activity of the genes responsible for correcting errors. When its level becomes abnormal, this control goes awry. Surprisingly, too much correction can become problematic. Excessive activity of the repair system ends up damaging the DNA instead of protecting it. Balance is therefore essential to maintain a stable genome.

This instability could explain some damage observed in neurons, causing neurological diseases.

By analyzing data on different cancers, the scientists also observed a clear trend here. Cells with high levels of TDP43 also contain more mutations. This reinforces the idea that this protein plays a central role in genome stability. Laboratory experiments provide an encouraging clue: by reducing the excessive activity of the repair system, the researchers managed to limit some of the damage caused by the dysregulation of TDP43.


These results open the way to new therapeutic approaches. Better understanding this delicate balance could help fight certain brain diseases, but also other pathologies linked to DNA mutations like cancer.

How does DNA repair work?

Our cells divide continuously to ensure the renewal of our tissues. With each division, all of our DNA, which contains our genetic code, must be copied with very high precision. However, this operation is not infallible and errors, called mismatches, can slip in, somewhat like a mis-copied letter.

To remedy this, cells have a built-in control device, a kind of automatic spell-checker. This system is formed by a set of specialized proteins that inspect the new DNA copy as soon as it's synthesized. They spot 'typing' errors, meaning the base pairs that don't assemble correctly according to the rules of DNA.

Once the error is identified, these proteins trigger a correction process. They excise the small section of DNA containing the mistake and replace it with the exact sequence, using the original DNA strand as a template. This operation is essential to preserve the integrity of our genes across cellular generations.

If this mechanism works poorly, errors accumulate. These mutations can remain silent, but they can also alter the function of important genes, sometimes leading to cellular dysfunctions. Maintaining this process in good working order is therefore an important element for the long-term health of our cells and our organism.