PULLMAN–A suite of proteins that changes the arrangement of DNA in chromosomes plays a key role in enabling cells to repair damage to their DNA, according to a new study by researchers in Washington State University’s School of Molecular Biosciences.
The report, by scientists Feng Gong, Deirdre Fahy, and Michael Smerdon, offered the first direct proof of a link between the DNA-remodeling proteins and DNA repair proteins in whole cells.
“We and others had done similar work in vitro [in cell extracts],but this was the first demonstration of it in living cells,” Sherdon said.
Their paper was named “Article of the Month” in the October 2006 issue of Nature Structural and Molecular Biology.
The researchers exposed yeast cells to ultraviolet radiation to create lesions in the DNA-modifications of the genetic code that, if not corrected, become mutations that can cause a variety of life-threatening conditions. They then studied the actions of several proteins associated with the DNA.
Smerdon said that in humans, each cell in the body sustains between 10,000 and 20,000 DNA lesions every day, just as a result of normal metabolic activity.
“Those come regardless of whether we smoke or not, regardless of whether we have an x-ray, regardless of whether we’re a suntanner or not,” Smerdon said. “The bottom line is that you and I would fall apart very quickly if we did not have DNA repair.”
In order to repair lesions in the DNA, a cell must first recognize them and then replace each damaged portion with an undamaged or ‘correct’
version. The process is especially challenging because DNA in living cells is not the long, bare strand we see in biology textbook diagrams. It is wrapped around specialized DNA-binding proteins in a way that enables it to fit inside the cell’s nucleus, but that also limits access by the repair machinery.
Smerdon’s lab has spent years exploring how the tightly-packaged DNA is “remodeled” to allow it to function normally and to be repaired. Other researchers had previously identified a complex of about 11 proteins, called SWI/SNF (pronounced “swigh-sniff”), that changes the shape and arrangement of DNA with its associated structural proteins. Also, other proteins had previously been shown to function in identifying lesions on the DNA.
In the current study, he and his group looked for a link between SWI/SNF and the repair machinery, and whether remodeling by SWI/SNF is an important part of the repair process. They found that in yeast cells undergoing high rates of DNA repair, SWI/SNF is physically attached to two of the key proteins involved in recognizing damage sites on the DNA. They further found that when they “knocked out” the SWI/SNF complex, the cells lost much of their ability to remodel DNA and to repair damaged areas. When SWI/SNF was restored to normal, the cells regained their ability to remodel and repair their DNA.
The group is now doing experiments with human cells, which contain a SWI/SNF complex that appears to function in much the same way as the yeast complex.
Their work was supported by the National Institutes of Health and the American Cancer Society.
For more information, visit
http://www.nature.com/nsmb/journal/v13/n10/full/nsmb1152.html.
