Jumpstarting DNA repair. (Genetic Research).Every day, your 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. suffers damage--ultraviolet radiation, pollution, and cigarette smoke all take their toll. If unchecked, this damage can produce more extensive DNA lesions that result in tumors. Fortunately, DNA continuously repairs this damage. Now, for the first time, scientists have identified a protein that senses DNA damage from ultraviolet radiation and may trigger the repair process, known as the DNA damage checkpoint system. A team from the University of North Carolina at Chapel Hill The University of North Carolina at Chapel Hill is a public, coeducational, research university located in Chapel Hill, North Carolina, United States. Also known as The University of North Carolina, Carolina, North Carolina, or simply UNC have found that a protein named ATR ATR Achilles tendon reflex, see Ankle reflex directly binds to DNA. Their study, published in the 14 May 2002 issue of Proceedings of the National Academy of Sciences The Proceedings of the National Academy of Sciences of the United States of America, usually referred to as PNAS, is the official journal of the United States National Academy of Sciences. , adds to scientists' broad knowledge about cancer and how cells protect themselves from DNA damage. "The DNA damage checkpoint system is really what determines cell death or survival, in both normal cells and cancerous cells," says principal investigator Aziz Sancar, a professor of biophysics biophysics, application of various methods and principles of physical science to the study of biological problems. In physiological biophysics physical mechanisms have been used to explain such biological processes as the transmission of nerve impulses, the muscle and biochemistry. "ATR is a key protein in understanding this system." Scientists already knew that ATR was somehow involved in the damage checkpoint system, but some had speculated that an intermediary protein actually sensed the damage. "We demonstrated that, without an intermediary, ATR binds to DNA, and when there is DNA damage [ATR] binds with higher affinity," says Sancar. "It is the first biochemistry paper showing that this protein has affinity for damaged DNA and can sense the damage directly." The researchers purified ATR from human connective tissue cells, then mixed the purified ATR with both damaged and undamaged DNA. They then measured the binding using different methods of biochemical analysis as well as electron microscopy. In one method, the researchers bound the ATR to carbohydrate beads, added radiolabeled DNA, washed the beads three times to eliminate unbound unbound said of electrolytes, e.g. iron and calcium, and other substances which are circulating in the bloodstream and are not bound to plasma proteins so that they are available immediately for metabolic processes. See also calcium, iron. DNA, and then visualized the ATR-bound DNA by autoradiograph au·to·ra·di·o·graph n. An image recorded on a photographic film or plate produced by the radiation emitted from a specimen, such as a section of tissue, that has been treated or injected with a radioactively labeled isotope or that has absorbed or . Measuring the radioactivity indicated the amount of DNA bound to the ATR. The findings all showed that ATR bound directly to DNA, and bound with twice the affinity to damaged DNA. The authors call the twofold difference in binding modest, but Jim Drummond, an assistant professor of biology at Indiana University Bloomington who specializes in the mechanisms of DNA repair pathways, says that small differences found during in vitro in vitro /in vi·tro/ (in ve´tro) [L.] within a glass; observable in a test tube; in an artificial environment. in vi·tro adj. In an artificial environment outside a living organism. experiments can be significant in vivo. "When you look in the cell, those sort of small [DNA-level] differences can be amplified into very large [organism-level] differences," he says. According to Drummond, the next logical step is to identify the specific sequence of cellular signals that make up the checkpoint system--how ATR's binding to damaged DNA results in a change in the cell cycle and the actual repair of the DNA. Understanding that sequence could eventually provide researchers with dues to possible gene targets for drugs or other therapies. |
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