For the first time ever, researchers have shown that a key DNA repair protein is intimately involved in protecting telomeres, the end caps of chromosomes. The work by researchers at City of Hope and beyond may offer new insights into cancer and other diseases, as well as aging.
 Bing Shen (Photo by Fred Lee) |
Chromosomes consist of DNA and contain all of the genes that guide the growth, development and normal life processes of cells. As cells grow and divide, they must make new copies of each chromosome. When the cell splits, each new cell takes a full complement of chromosomes with it.
Telomeres normally prevent chromosomes from unraveling when a cell makes copies of them. They also keep chromosomes from accidentally linking together, which can cause genetic mutations that lead to disease or death.
Telomeres tend to shorten over time as cells grow and divide multiple times. Researchers believe this shortening affects aging and can increase risk of genetic disease.
Cells counter telomere shortening with an enzyme called telomerase, which works to re-build and repair telomeres.
Binghui Shen, Ph.D., professor and associate chair of the Department of Cancer Biology, and a team of researchers found that a protein called FEN-1 works closely with telomerase to help keep telomeres healthy.
FEN-1 is an enzyme that helps repair DNA following damage by toxins, radiation or mistakes in duplication during cell division.
“FEN-1 links up with telomerase and tells it when it needs to be active in rebuilding telomeres,” said Shen.
Shen has studied FEN-1 for years and was the first to show how it contributes to DNA repair.
“This is the first time anyone has shown the connection between FEN-1 and telomerase,” he said. The work sheds more light on how cells keep telomeres healthy — an area of some mystery — and one day could lead to telomerase-based cancer therapies.
The study conducted with researchers from Washington State and Texas Woman’s universities appeared in the Feb. 6 issue of the Journal of Biological Chemistry. It was supported by the National Institutes of Health and Texas Woman’s University.
