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Studying the fundamental aspects of biology can sometimes lead to unexpected findings that directly relate to human disease. In one of the latest examples of scientific serendipity, researchers from the Salk Institute found that an important quality control mechanism in baker's yeast is closely connected to hypomyelinating leukodystrophy, a debilitating disease found in children.
The findings, reported September 7, 2018, in the journal eLife, could indicate a therapeutic approach for this rare disease, as well as for multiple sclerosis and other neurodegenerative diseases.
Coincidence - Discovery - Cancer - Society - Professor
"It's a total coincidence that we made this discovery," says Salk American Cancer Society Professor Tony Hunter, the paper's senior author. "We wouldn't have guessed that this yeast protein would play a role in human disease in this way."
In the face of genetic damage—from cancer or other diseases—cells mobilize molecular processes that act as repair crews. For the past decade or so, one focus of Hunter's lab has been the study of certain proteins that regulate these repair procedures through a process called sumoylation. SUMO addition to proteins, or sumoylation, acts as a quality-control mechanism to signal to a cell that the protein should be cleared out.
Study - Salk - Research - Associate - Zheng
In the current study, Salk Research Associate Zheng Wang, the paper's first author, set up a genetic screening test in yeast to determine which proteins relied on sumoylation to function properly. He identified several subunits of a protein complex called RNA polymerase III—which plays an important role in copying DNA into RNA—among those that were affected. The team found that when Pol III was mutated the cells stop growing, because the mutant Pol III cannot make enough transfer RNAs (small RNAs that are needed for cells to synthesize proteins). However, that defect could be rescued by reducing sumoylation in the yeast...
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