Reporting in Nature, scientists have identified a novel process that protects the ends of chromosomes from incorrectly applied DNA repair. Although DNA repair is a crucial mechanism that can protect a cell from serious harm, it should not happen at the ends of chromosomes, which are known as telomeres. Telomeres are special caps that shield the ends of chromosomes from degradation. If DNA repair mechanisms happen there, it can have major consequences for cells. These new insights may have implications for our understanding of cancer and some rare disorders.
A variety of problems can arise in DNA; a mutation might happen when DNA is being replicated for cell division; or UV rays can harm genomic DNA, for example. Cells can often repair minor DNA damage, and will move quickly to do so.
When the DNA helix simply ends, that is typically an indication of a serious problem. But chromosomes naturally come to an end, and they should never be fused to more DNA. If the ends of a cell’s chromosomes were ‘fixed’ by being joined to the end of another chromosome, that cell could become cancerous.
Telomeres are a kind of cap that can both keep the ends of chromosomes from degrading, as well as shield those ends from the cell’s DNA repair processes.
"What's the difference between damaged DNA and the natural chromosome end? This problem has been known for almost a century, but some aspects are still not completely resolved," noted study co-author Francisca Lottersberger, an associate professor at Linköping University.
Some DNA repair proteins hang around the ends of chromosomes. Previous work by this team revealed that the repair molecule DNA Protein Kinase (DNA-PK) helps prevent degradation at telomeres.
Now this work has shown that two other proteins: RAP1 and TRF2 help regulate DNA-PK. "We show genetically, biochemically and structurally how the protein RAP1, brought to telomeres by TRF2, ensure by direct interaction that DNA-PK doesn't repair the telomeres," said Lottersberger.
There are a few diseases that can arise when telomere maintenance becomes dysfunctional, such as aplastic anemia, premature aging, and fibrosis in the lungs. These can happen when there are genetic mutations that disrupt telomeres, but those cannot explain all of the cases. This study could help researchers learn more about why those diseases happen in the absence of telomere disruption.
Sources: Linköping University, Nature
