Werner Syndrome Essay Research Paper AbstractNowadays those — страница 3

  • Просмотров 305
  • Скачиваний 5
  • Размер файла 20

acids, does not exactly match anything else in the databases. But because part of it closely resembles the sequences of genes that code for known helicases, Schellenberg and his colleagues assume this gene, too, codes for one, although they have not proven that directly. Assuming that it does, however, that “tells you straight away that there are DNA transactions that are important [for Werner syndrome],” says S. Michael Jazwinski, a molecular geneticist at Louisiana State University Medical Center in New Orleans. Exactly what kind of transaction it still remains unclear. There exist a half-dozen or so known helicases that unwind the DNA, and prepare the way for DNA replication or repair, gene expression, chromosome recombination, as well as the shuffling of chromosomal

segments that takes place during formation of the germ cells. Derangement in any of these processes has the potential to damage the genetic material, and thus the cell. This in turn could cause cells to function poorly, causing premature aging associated with Werner syndrome. If the DNA damage happened to inactivate tumor suppressor genes or active oncogenes, it might also cause cells to grow out of control and produce cancerous tumors. In fact, there is already evidence that a faulty helicase can cause cancers. Recently a team led by geneticist James German of the New York Blood Center in New York City pinpointed the gene for Bloom’s syndrome, another rare disease associated with several cancers and numerous chromosome abnormalities, and it, too, specifies a helicase. Still

unclear, however, is why a helicase mutation would cause the unusual cancers seen in Werner syndrome patients. Most cancers arise in epithelial tissue-the skin or the linings of the colon and lungs and of the mammary ducts. But in the April issue of Cancer Epidemiology, Biomarkers and Prevention, Japanese and U.S. researchers, including Miller, report that the cancers associated with Werner syndrome are just as likely to develop in nonepithelial tissue, such as muscles and connective tissue. But before researchers can explore this issue or pursue analogies between the Werner syndrome gene and known helicase genes, they will need to test the hypothesis that it really does code for a helicase. The reason for this caution is that the capacity of the WRN protein to act as a helicase

has yet to be demonstrated and there are several other genetic diseases resulting from mutations in genes encoding DNA helicases that do not resemble Werner syndrome. Xeroderma and Cochayne syndrome, which also result from defective DNA helicases, result in increased sensitivity of cells to ultraviolet radiation. This is thought to happen because ultraviolet rays damage DNA, which cannot be properly repaired by the mutant helicases. Yet, Werner syndrome cells are not abnormally sensitive to ultraviolet radiation. In short, it is known that defects in a presumed DNA helicase are the cause of Werner syndrome, but is not know how this defect results in the disease. The next step is to explore what effects, if any, mutations in the WRN gene have on DNA repair or other aspects of DNA

metabolism. Still, as Schellenberg cautions, answering these questions will not explain everything about aging. “I don’t want to sell Werner syndrome as a total mimic of aging,” he emphasizes. He also notes that there are some essential differences between how people with Werner syndrome age and the way everyone else ages and not just in the kinds of cancer, they suffer from. Although prematurely old, the patients do not develop Alzheimer’s disease or high blood pressure, diseases, which are typically associated with old age. Instead, they experience symptoms not associated with normal aging such as ulceration of the skin, particularly around the ankles, alteration of the vocal chords resulting in a high-pitched voice, and an absence of the growth spurt that normally

occurs after puberty. Even if the gene does play a role in normal aging, it cannot be acting alone. Researchers estimate that some 70% of human genes are involved in some way in determining how long people live. It is possible that the most valuable piece of information gained is knowing the identity of the Werner syndrome gene and that it may allow the development of an animal model for studying the disease. Researchers have not yet determined whether it is possible to create a mouse, which as the genetic equivalent of the WRN gene and that contains the same mutation that causes Werner syndrome in humans. Researchers are also unsure whether the mutation would produce accelerated aging in the mouse because aging is such a difficult process to understand, and that the primary