Cells in the human body are constantly dividing. Whenever cells divide into two, the DNA within them must be copied as well. Most of the time this process works as planned, but some times the DNA can be copied incorrectly. Other factors such as UV rays and radiation can damage DNA and lead to problems like cancer. While these errors in DNA copying can cause significant mutations, they are usually corrected by certain proteins within the cell. New research at the University of Michigan is allowing scientists to get a better idea of how these proteins go about finding the damaged sites and repairing them.
In this study, researchers at UM examined the MutS protein in bacteria. According to Lyle Simmons, associate professor of molecular, cellular, and developmental biology at UM, it has been known for a long time that the MutS protein could find and repair errors in DNA. “MutS is the first protein involved in DNA mismatch repair and is responsible for detecting rare errors that can predispose people to certain types of cancer, a hereditary condition called Lynch syndrome or cancer family syndrome. If a person’s mismatch repair system is hindered, the mutation rate increases 100-to-1,000 fold” says Simmons. Despite knowing what these proteins do, it remained unclear as to how they perform these tasks.
To see how the protein works, researchers “fused the MutS protein to a fluorescent tag and activated fluorescence with a laser.” They then studied the protein’s actions inside of a bacterial cell. Tagging the proteins with fluorescence allowed researchers to track its movement through the cell. Scientists observed that MutS moved quickly through the nucleoid but slowed down at DNA replication sites. This indicates that the proteins look for sites of replication rather than individual mismatches. The protein then searched the new DNA being created for errors. Mismatches occur when the wrong nitrogenous bases are paired with each other. “The mismatched pair kinks the DNA at the replication fork where DNA is made. MutS positions itself at that fork so it’s ready to catch any mistakes. As an added bonus, this positioning likely tells MutS which side is correct and which side is the new, altered DNA.” says Julie Biteen, assistant professor of chemistry.
Despite the study being performed on bacteria, it is very likely that the same process occurs in human cells. This discovery is very important because it provides information that will be essential to learning more about how the body responds to mutations. Further advances in this area of study could possibly help researchers understand cancer better.
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