By studying the yeast used to make beer and bread, scientists have discovered the mechanism ancient proteins use to repair damage DNA—and how their dysfunction can lead to the development of tumors.
In humans, protein mutations called RAD51 paralogues have been associated with breast and ovarian tumors.
Researchers say their findings could lead to new ways to tailor cancer therapies.
“These are proteins that have been present throughout evolution in many species, but very little has been known about what they do,” says Kara Bernstein, assistant professor of microbiology and molecular genetics at University of Pittsburgh School of Medicine.
“Our study shows for the first time the mechanism of how they are involved in the repair of damaged DNA.”
Because RAD51 paralogues are too difficult to work with in animal cells, researchers instead explored their function in yeast. They found the proteins interact with other proteins called the Shu complex to repair breaks in DNA strands, which can be caused by environmental toxins, radiation, and other naturally occurring exposures.
The findings, published in Nature Communications, show that Shu complex works synergistically with additional RAD51 paralogues to search for homologous, or complementary, DNA regions with double-strand breaks, in which both poles of the twisting DNA ladder have been broken.
Pieces of the genetic code can be lost in such areas; the paralogues and complex repair the damage by filling in the missing pieces in a process called homologous recombination.
“Now that we understand what the proteins do, we can perhaps tailor therapies for patients who have cancer and mutations in these repair genes,” Bernstein says.
Other researchers from the University of Pittsburgh and from Yale University are coauthors of the study. The National Institutes of Health funded the work.
Source: University of Pittsburgh