Programmed DNA Break and Telomeres Study Published
Research in the Department of Biochemistry and Cellular and Molecular Biology is providing insights into DNA break and repair processes necessary for the development of a human parasite.
A recently published study led by graduate student Brandon Estrem determined when and where DNA breaks appear during the development of the human and pig parasite Ascaris, which infects over 700 million people worldwide. This work was performed at the University of Tennessee, Knoxville, with support from the National Institutes of Health.
DNA double-strand breaks (DSBs) are the most severe form of DNA damage. If DSBs aren’t properly repaired, they can lead to disease. DSBs are typically repaired by joining the broken pieces with little or no changes. However, some DSBs can be repaired by the addition of telomeres, the repetitive sequences that cap the ends of chromosomes. This type of repair often leads to loss of sequences and is most often found in cancer cells.
However, some organisms undergo a similar process called programmed DNA elimination (PDE). PDE declutters the genome by making DSBs at precise genomic locations, resulting in the loss of DNA. Notably, the DSBs are healed with telomere addition.
To better understand the processes associated with PDE, researchers in the Wang Lab used state-of-the-art genomics and bioinformatics, to identify where DSBs occur in the genome. Their data also revealed how the broken ends are processed before they are healed with telomere addition.
This work was recently published in Nucleic Acids Research. It was also selected for an oral presentation at the Molecular Parasitology Meeting in Woods Hole, Massachusetts, and presented as a poster at the Allied Genetics Conference in Washington, D.C.
Now Estrem and the team are trying to understand how the cell recognizes and makes the breaks. “What proteins are breaking the DNA, and how are they finding this spot in the genome compared to anywhere else?” he explained.
“As a kid, I liked to take things apart and understand how they worked, and that’s still true today,” he said. “I like to see how things work, understand them, and that’s a lot of what science is.”
He relishes that moment of discovery, being the first to figure out what is happening before writing it up and sharing it with the world.
By Amy Beth Miller