When the gene for WRN is defective the result is Werner's syndrome, a rare inherited disease that shows no symptoms until puberty but soon causes rapid aging. Beginning in their twenties, victims may become afflicted with cataracts, hair loss, wrinkled skin, osteoporosis, arteriosclerosis, and type II diabetes; many patients contract cancer, and most die by the age of 50. Understanding how the WRN protein normally works to maintain genomic integrity could lead to new forms of treatment for cancer and age-related pathologies.
"One reason we are particularly interested in WRN is because Werner's syndrome is unusual among premature-aging diseases, in that children are born normal and show no signs of disease until early adulthood," says Steven Yannone of Berkeley Lab's Life Sciences Division. "This gives us a better chance of clearly separating defects in development from aging."
"We wanted to study the protein itself because it is unique," says Jeff Perry of the Scripps Research Institute's Department of Molecular Biology and Skaggs Institute for Chemical Biology, formerly of Berkeley Lab, who led the research with Yannone. "WRN belongs to a family of enzymes called RecQ helicases" -- of which there are five in the human genome, performing important functions in DNA replication, recombination, and repair -- "but in this family, only WRN has coupled a helicase function and a nuclease function within the same protein."
Helicases open up the double helix of DNA, while nucleases degrade one or both of the DNA chains; both operations are critical to repairing errors and proofreading DNA sequences. One part of WRN is an exonuclease, which starts working from the end of a DNA str
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Contact: Paul Preuss
paul_preuss@lbl.gov
510-486-6249
DOE/Lawrence Berkeley National Laboratory
23-Apr-2006