The ability to create a tailor-made cancer therapy to target specific tumors could revolutionize treatments. Scientists from the University of Pittsburgh School of Medicine have been studying proteins in the yeast used to make beer and bread in a search for these “silver bullet” therapies.
The ancient proteins, known as “RAD51 paralogues” are involved in cancer predisposition and human disease. They are particularly associated with human breast and ovarian tumors. But cancer research in this field has been problematic because RAD51 paralogues are too difficult to work with in animal cells. As a result, scientists didn’t even know if Rad51 mediators function independently or in a cooperative manner. So the Pittsburgh team turned to yeast for their study.
How the ancient proteins can damage or repair
The research helped the team understand how dysfunction in the proteins can lead to the development of tumors. But, crucially, they also discovered the mechanism by which the proteins repair damaged DNA.
“These are proteins that have been present throughout evolution in many species, but very little has been known about what they do. Our study shows for the first time the mechanism of how they are involved in the repair of damaged DNA,” said Kara Bernstein, assistant professor of microbiology and molecular genetics at Pittsburgh.
Bernstein and colleagues found the RAD51 paralogues proteins interact with other proteins called the “Shu complex” to repair breaks in DNA strands. Such DNA damage can result from environmental toxins, radiation, and other naturally occurring exposures.
Mending the broken DNA ladder
The paper, “Promotion of presynaptic filament assembly by the ensemble of S. cerevisiae Rad51 paralogues with Rad52,” appears in the journal Nature Communications. It describes how 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.
In these damaged areas, pieces of the genetic code can be lost. The paralogues and Shu complex home in to the “broken ladder” and 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,” said Bernstein.
Other researchers from the University of Pittsburgh and from Yale University are co-authors of the study. The National Institutes of Health funded the work.
This article used material from the University of Pittsburgh School of Medicine under the Creative Commons license.
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