Scientists are now one step closer to understanding how and where DNA mutations occur, at least those that happen naturally.
A team of researchers at the University of Edinburgh, Scotland, recently tracked DNA, specifically looking at how it replicates when cells divide. They discovered patterns in how mutations occur, as well as learning where mutations are most likely to appear.
Researchers figured out how to label and keep track of specific pieces of DNA, particularly new pieces, and learned to follow the enzyme responsible for copying those pieces. Their research focused on enzymes called polymerases. These enzymes create small regions in DNA that act as scaffolds for the copied DNA.
Scientists assumed that the body deletes the scaffolds containing errors, or mutations and the standard computer models supported this theory. However, the actual research showed that about 1.5 percent of those erroneous scaffolds are left over, trapped within the DNA.
After running models, scientists now believe they can track how DNA replicates and find the most likely areas where these scaffolds with errors turn up. They discovered that these erroneous scaffolds usually appear close to genetic switches, those regions that turn on when genes activate. The mutations damage the switch, which results in genetic disease, as well as increasing the likelihood of cancer.
"This shows us that despite DNA replication being an amazingly accurate process, errors do occur that cluster at important sites in the genome," says Professor Andrew Jackson, MRC Human Genetics Unit, University of Edinburgh. "This new insight into a fundamental biological process has been made possible by combining cross-disciplinary computational and laboratory expertise at the IGMM."
Researchers hope that knowing where to look for naturally occurring genetic mutations could lead to understanding diseases related to such mutations. For example, people with mutations in the BRCA1 and BRCA2 genes are more susceptible to breast cancer. Actress Angelina Jolie had her breasts removed several years ago after testing positive for a mutation in the BRCA1 gene.
"We have been aware of striking patterns in how DNA changes for several years but couldn't explain why the patterns were there," says Dr. Martin Taylor, MRC Human Genetics Unit, University of Edinburgh. "This new work gives us a mechanism and revealed previously unseen patterns that are probably the most important finding, as they point to sites in our DNA that are likely to have a high rate of damaging mutations."