Our DNA is arranged into chromosomes that carry a kind of protective shield at their ends, called telomeres. These protective caps are crucial to the stability of chromosomes, and when telomeres become dysfunctional, serious disorders, like certain types of cancer, or bone marrow disorders can arise. Now scientists have identified a problem in a protein that is crucial to telomeres, and which could relate to a variety of diseases. The findings have been reported in Science.
Telomeres naturally get shorter every time a cell divides, so they shorten as we age. But problems with telomere formation or maintenance can cause problems such as premature aging.
In new research, scientists used a computational tool called AlphaFold to predict the protein interactions and protein structures that are relevant to telomeres. This work identified a molecule known as replication protein A (RPA), which seems to be crucial to telomere maintenance, because it stimulates telomerase.
Although scientists have previously revealed the connection between RPA and DNA repair, this research indicated that it is essential to telomere maintenance as well.
After AlphaFold identified RPA, the researchers confirmed their finding in experiments with human cells. This showed that RPA is essential to telomere stimulation and maintenance.
"This line of research goes beyond a biochemical understanding of a molecular process. It deepens clinical understanding of telomere diseases," noted Ci Ji Lim, a University of Wisconsin–Madison professor of biochemistry.
This work may have implications for people with illnesses that are known to be caused by aberrant telomere shortening such as aplastic anemia, acute myeloid leukemia, and myelodysplastic syndrome.
"There are some patients with shortened telomere disorders that couldn't be explained with our previous body of knowledge," said Lim. "Now we have an answer to the underlying cause of some of these short telomere disease mutations: it is a result of RPA not being able to stimulate telomerase."
Sources: University of Wisconsin–Madison, Science