Proteasome may help remove UV damage blocking gene translation

Scientists at UT Southwestern have uncovered a novel role for a cluster of proteins that normally disposes of unwanted proteins in a cell.

Normally a large cluster of proteins called the proteasome recognizes other proteins that have been tagged for disposal and destroys them. In a recent study, UT Southwestern researchers found that the proteasome may also help remove obstructions that interfere with a cell's ability to properly translate its genetic code.

The findings were reported in the April 20 issue of Proceedings of the National Academy of Sciences and are available online.

"It used to be that the proteasome was thought of as this monolithic thing with a single function, but now we see that it is very versatile, and can also work to clear up roadblocks in gene transcription," said Dr. Tom Kodadek, professor of internal medicine and a senior co-author on the study.

Information contained in genes is used to make various proteins, which then carry out vital functions in the body. The first step in translating genetic information is called transcription, where special proteins travel the length of a gene, "reading" the genetic code. The transcription machinery uses the information to make RNA molecules, which in turn manufacture new proteins.

Normally, when the transcription mechanism reaches the end of the gene, it hits a stop signal contained in the gene and stalls.

Dr. Kodadek and colleagues discovered that the proteasome is found at the ends of genes that are actively being transcribed. As the transcription machinery accumulates on the ends of genes, the amount of the proteasome also increases. This suggests that the proteasome may be involved in terminating the transcription of that gene.

The study results also show that the proteasome is found at sites of ultra violet-damaged DNA. UV-exposed DNA is difficult to read and transcribe, so the transcription machinery stops at the damaged sections and builds up. The amount of proteasome also in creases at sites of UV damage, where it interacts with the transcription machinery.

"We believe that the proteasome clears the roadblock at these DNA damage sites, possibly allowing the cell's DNA repair machinery to reach the site and repair the lesion," Dr. Kodadek said.

Other contributors to the study are Dr. Thomas Gillette, postdoctoral researcher in internal medicine; Dr. Fernando Gonzalez, former graduate student; Dr. Agnes Delahodde, visiting scientist; and senior co-author Dr. Stephen A. Johnston, director of the Center for Biomedical Inventions.

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Megha Satyanarayana
214-648-3404
Megha.Satyanarayana@utsouthwestern.edu

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