An international study used electron cryomicroscopy to explain how the MutS protein, considered the “guardian” of the genome, repairs possible errors in DNA during cell division.
National Cancer Research Center (CNIO) It has been discovered how certain proteins ensure Repair errors caused by DNA during replication. Use electronic cryoscopy to check, Rafael Fernandez Leiro Make visible Protein mutation, Also known as the “gatekeeper” of our genome, which allows them to describe how this single protein coordinates this important DNA repair process from start to finish.
The research is related to Med Lammers, Leman University Medical Center, LUMC (Netherlands) and Titia Sixma, From the Netherlands Cancer Institute and Oncode Research Institute.Their results are published in Natural structure and molecular biology.
Between different stages Cell division There is DNA replication, during which DNA polymerase replicates the genetic information of the cell to transfer it to daughter cells. Although the mechanism is very precise, errors occasionally occur. These errors must be repaired, otherwise it will cause tumors.
Researchers have described in previous work that DNA polymerase has its own corrector, an exonuclease, which allows it to correct errors introduced during DNA replication. However, when the corrector is insufficient, the MutS protein will enter the scene, scan the copied DNA for errors, and then initiate and complete the repair of those proteins it detects.
It’s not clear until now How does a single protein coordinate so many different processes. “We can observe it as it performs its function and capture its molecular structure in a continuous conformation.” With this information, we have been able to understand how individual proteins coordinate the entire process, which must be extremely precise,” explains Fernández-Leiro .
How mutations develop
An in-depth understanding of our DNA repair process, which involves DNA polymerase itself, exonuclease and MutS protein, is essential for understanding how changes in any of these proteins lead to mutations and therefore many mutations. Increased risk of certain types of tumors, For example, Lynch syndrome or endometrial cancer.
Researchers insist that electron microscopy plays an important role in revealing protein structure. “Electron cryomicroscopy allows proteins to obtain very high-resolution images as they perform their functions. Using these images, we can reconstruct the three-dimensional structure of the protein in a computer and generate atomic models to understand how it works,” Fernández- Leiro concluded.
Rafael Fernández-Leiro and others. “The selection process of selecting DNA mismatches for repair”. Natural structure and molecular biology, 2021. DOI: 10.1038 / s41594-021-00577-7
The research was funded by the Ministry of Science and Innovation, Carlos III Health Institute, National Innovation Agency, British Medical Research Council, Oncode Institute, NWO-Gravity and Horizontes 2020.