The role of the gene of the Cockayne Syndrome in the repair of oxidative DNA damage. (News Briefs).Cockayne Syndrome (CS) is a human genetic disorder with diverse clinical symptoms that include hypersensitivity hypersensitivity, heightened response in a body tissue to an antigen or foreign substance. The body normally responds to an antigen by producing specific antibodies against it. The antibodies impart immunity for any later exposure to that antigen. to sunlight, severe mental and physical growth retardation, progressive neurological and retinal degeneration, and skeletal abnormalities. It has two complementation Complementation (genetics) The complementary action of different genetic factors. The term usually implies two homologous chromosomes or chromosome sets, each defective because of mutation and unable by itself to promote the normal development or metabolism of groups, CS-A and CS-B. The gene of CS-B encodes a protein (CSB CSB Kashubian (SIL code, Poland) CSB Chemical Safety and Hazard Investigation Board CSB Chemical Safety Board (Washington, DC) CSB Community Services Board CSB Computational Systems Bioinformatics protein), which is known to play a role in the cellular repair of DNA DNA: see nucleic acid. DNA or deoxyribonucleic acid One of two types of nucleic acid (the other is RNA); a complex organic compound found in all living cells and many viruses. It is the chemical substance of genes. damage, but it may participate in other pathways of DNA metabolism. NIST (National Institute of Standards & Technology, Washington, DC, www.nist.gov) The standards-defining agency of the U.S. government, formerly the National Bureau of Standards. It is one of three agencies that fall under the Technology Administration (www.technology. researchers, in collaboration with scientists at the National Institute of Aging, NIH "Not invented here." See digispeak. NIH - The United States National Institutes of Health. Baltimore, investigated the role of the CSB protein in the cellular repair of oxidative DNA damage, which results from normal cellular metabolism and oxidative stress. Transformed human cell lines with site-directed mutations in the CSB gene were established. These cell lines were then used to study phenotypical changes affected by the mutations, including DNA repair by whole cell extracts and the accumulation of oxidative DNA damage in genomic DNA of cells after exposure to oxidative stress. Cells were exposed to low doses of ionizing radiation to cause oxidative stress. Researchers found that the mutant cells and those with the deleted CSB gene had greater sensitivity than wild-type cells to ionizing radiation. The mutant cells had lower activity of DNA repair as shown by determination of activities of DNA repair enzymes. The results showed that the biological functions of the CSB protein in DNA repair might be mediated by distinct functional motifs of the protein. In addition, the accumulation of two well-known products of oxidative DNA damage in genomic DNA was measured using liquid chromatography-mass spectrometry Liquid chromatography-mass spectrometry (LC-MS) is an analytical chemistry technique that combines the physical separation capabilities of liquid chromatography (aka HPLC) with the mass analysis capabilities of mass spectrometry. . These products accumulated to a greater extent in mutant cells and in cells with the deleted CSB gene than in wild-type cells after exposure of cells to ionizing radiation at 2 Gray. Taken together, this study suggests that the accumulation of oxidative stress-induced DNA lesions in genomic DNA of the CSB cells may contribute significantly to the pathogenesis of the human disorder Cockayne Syndrome. CONTACT: Miral Dizdar, (301) 975-2581; miral.dizdar@nist.gov. |
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