Sci. Aging Knowl. Environ., 20 October 2004
Arabidopsis might provide new insights into workings of protein linked to a premature aging disease.
R. John Davenporthttp://sageke.sciencemag.org/cgi/content/full/2004/42/nf93
COLD SPRING HARBOR, NEW YORK--Plants might not get gray hair and wrinkles, but they could enhance our understanding of a purported human aging protein. The botanical version of the protein might help clarify the molecule's connection with decrepitude, scientists reported here on 7 October 2004 at the Molecular Genetics of Aging meeting.
Patients with Werner syndrome show some signs of accelerated aging: For instance, early in life, their skin wrinkles, their hair turns gray, and they suffer from heart disease and cancer. Affected individuals typically die in their 40s (see "Of Hyperaging and Methuselah Genes"). The disease stems from mutations in a gene that produces WRN, a protein that untwists DNA and chews up its strands; those capabilities help keep chromosomes intact. For instance, some studies suggest that faulty WRN renders chromosomes susceptible to breaks and swapped segments, especially at their ends (see "A Twist in an Early End"). Researchers have investigated how WRN behaves in the test tube (see Fry Review), but they don't completely understand how it functions in the cell (see Monnat and Saintigny Review). Because plugging variants of the WRN gene into rodents is difficult, biochemist Lucio Comai of the University of Southern California in Los Angeles and colleagues investigated whether Arabidopsis thaliana, an easily manipulated weed commonly used in genetic studies, might help reveal WRN's secrets in an intact organism.
In Arabidopsis, WRN's jobs appear to be divided between two proteins: One unwinds DNA and another whittles it. The team unearthed a line of plants with a glitch in the gene for the destruction protein. They purified the enzyme from those plants, as well as the normal protein from unmarred plants. The normal enzyme dissolved DNA in a test tube, whereas the abnormal one couldn't. Adding the proteins Ku70 and Ku80 to the mix amplified the normal enzyme's activity, as they do to the mammalian protein, but they had no effect on the faulty protein. Further experiments suggest that the mutant plants are unusually susceptible to DNA damage. The results hint that the plant proteins work similarly to mammalian WRN, and thus Arabidopsis might flower as a system for understanding WRN's function in whole organisms. Next, the researchers want to show that the DNA-unwinding protein collaborates with the DNA-shaving molecule, and to find out how the mutation alters the plant's physiology.
Although the botanical approach has just germinated, it might eventually provide new information about how WRN operates. For instance, plants possess a stock of stem cells in the tips of their shoots. Arabidopsis might help scientists determine whether WRN-like proteins are crucial for the health of stem cells, says molecular biologist Judith Campisi of Lawrence Berkeley National Laboratory in California. Studying the weed might help fertilize new ideas about aging.
October 20, 2004
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