Four structures of the “gene protector” protein at work under the electron microscope.
For the first time, a study has observed a protein that intervenes to help repair human DNA when the replication process goes awry, with important implications for tumor research.
Accurate replication of DNA is a fairly important part of the human cell division process, to ensure that the entire genome within the cell can be passed on to daughter cells intact. However, this process can sometimes go wrong, leading to some serious problems such as the creation of tumors. But the human body has its own mechanism for error correction.
What scientists previously knew was that a nucleic acid exonuclease (exonucleases) is involved in the repair mechanism, automatically correcting errors in DNA replication when they occur. In addition, a MutS protein also intervenes when this layer of error correction fails: it scans the DNA copy, finds the error, and is responsible for initiating and completing the repair. This is why this protein is also known as the “gene protector”.
This is quite astonishing work. Scientists wondered how this single protein could coordinate such a complex repair process.
The study, led by the Spanish National Cancer Research Centre (CNIO), used cryo-electron microscopy to see the process for the first time.
Study leader Rafael Fernández-Leiro said, “Using cryo-electron microscopy, we observed changes in the molecular structure of the MutS protein at each stage as it completes each function.”
The study describes that the DNA repair process involves a variety of factors including DNA polymerase, nucleic acid exonucleases and MutS proteins, and that the increased risk of cancers such as Lynch syndrome (a chromosomally related cancer) and endometrial cancer are associated with some of the changes that occur in these proteins. It is therefore important to understand more about the mechanisms by which these proteins work.
Fernandez-Lero says, “Only through electron microscopy can we take high-resolution images of the proteins during repair. From these images, we use computers to reconstruct the three-dimensional structure of this protein to build an atomic-level model that helps us understand how it works.”
The study was published April 5 in the journal Nature Structural & Molecular Biology.
Recent Comments