In the human body, DNA is constantly replicating its genes, creating duplicates that aren't always perfect. However, only some of those mistakes end up as mutations, and now, scientists know why: our DNA repair system focuses on some genes more than others.
Our body has its own "DNA spellchecker," a mechanism that repairs mistakes when they happen. However, scientists recently discovered that the repair system doesn't consider all genes equal: it focuses on some genes more than others, meaning that mutations happen where repairs don't occur.
Scientists at the EMBL-CRG Systems Biology Unit in Barcelona studied 17 million genetic mutations in the tumors of over 600 cancer patients by looking at "single nucleotide variants" within tumors. These are mutations that occur in just one nucleotide of DNA. This is important because this indicates that the mutation was not inherited, but happened within the body instead. This type of mutation is also the main cause of cancer, thanks to smoke, UV radiation and general mistakes made by our DNA copying sequences as we age.
These mutations happen more often in certain parts of the genome, so scientists wanted to know why. They discovered that the DNA spellchecker spends so much of its time fixing some replicated genes, that it's forced to ignore other genes.
"We found that regions with genes switched on had lower mutation rates. This is not because less mistakes are happening in these regions but because the mechanism to repair them is more efficient", says Ben Lehner, team leader and AXA professor.
Basically, the DNA spellchecker works efficiently with genes most necessary for important cell functions, but then becomes a little lazier with less important cells. Its capacity is limited, so it focuses its efforts where it's needed most. Unfortunately, that means that some unrepaired cells mutate and cause diseases such as cancer.
These researchers also discovered that switched on genes in tumors have fewer mutations than their switched off peers.
"The difference is not in the number of new mutations but in the mechanism that keeps these mutations under control," says Fran Supek, CRG postdoctoral researcher. "By studying cancer cells, we now know more about maintaining DNA integrity, which is really important for healthy cells as well."
This research, however, isn't just important for better understanding the causes of cancer. It could also lead to more knowledge about the process of aging, as well as the causes of genetic diseases.
