News
24/2/2015

CRG: ‘DNA spellchecker’ means that our genes aren’t all equally likely to mutate and cause disease

CRG: ‘DNA spellchecker’ means that our genes aren’t all equally likely to mutate and cause disease


News from CRG


Copying the large book that it is our genome without mistakes every time a cell divides is a difficult job. Luckily, our cells are well-equipped to proof-read and repair DNA mistakes. Now, Ben Lehner and Fran Supek, two scientists at the CRG, have published in Nature a study showing that mistakes in different parts of our genome are not equally well corrected. This means that some of our genes are more likely to mutate and so contribute to disease than others.

They analysed 17 million ‘single nucleotide variants’ – mutations in just one nucleotide (letter) of the DNA sequence – by examining 650 human tumours from different tissues. These were ‘somatic’ mutations, meaning they are not inherited from parents or passed down to children, but accumulate in our bodies as we age. Such somatic mutations are the main cause of cancer. Many result from mutagens, such as tobacco smoke or ultraviolet radiation, and others come from naturally occurring mistakes in copying DNA as our tissues renew.

The authors found that the ‘mismatch repair’ cellular machinery is extremely accurate when copying important regions containing genes that are key for cell functioning, but becomes more relaxed when copying less important parts. In other words, there appears to be a limited capacity for DNA repair in our cells, which is directed where it matters most.

More information:
CRG website

 

Reference:
Fran Supek and Ben Lehner, “Differential DNA mismatch repair underlies mutation rate variation across the human genome”, Nature, 23rd February 2015. DOI: 10.1038/nature14173