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Jumpstarting DNA repair. (Genetic Research).


Every day, your DNA suffers damage--ultraviolet radiation UV index predicts how long it would take a light-skinned American to get a sunburn if exposed, unprotected, to the noonday sun, given the geographical location and the local weather. It ranges from 1 (about 60 minutes before the skin will burn) to a high of 10 (about 10 minutes before the skin will burn).

A small amount of sunlight is necessary for good health.
, 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 have found that a protein named ATR ATR - A Territory Resource
ATR - Above the Rest
ATR - Above the Rim (Reebok)
ATR - Above Threshold Reporting
ATR - Above Top of Rail
ATR - Acceptance of TEMPEST Risk
ATR - Acceptance Test Report
ATR - Acceptance Test Review
ATR - Accord Type R (Honda Europe)
ATR - Action for Tinnitus Research
ATR - Action Taken Report
ATR - Advanced Tactical Radar
ATR - Advanced Telecommunications Research Institute International
ATR - Advanced Test Reactor
 directly binds to DNA. Their study, published in the 14 May 2002 issue of Proceedings of the 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
1. The study of biological processes using the theories and tools of physics.
2. The study of physical processes occurring in living organisms.

bio·physi·cal adj.
bi 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 DNA, and then visualized the ATR-bound DNA by autoradiograph
auto·radi·o·graphic adj.
auto·radi·og
. 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 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.
COPYRIGHT 2002 National Institute of Environmental Health Sciences
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2002, Gale Group. All rights reserved. Gale Group is a Thomson Corporation Company.

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Author:Spivey, Angela
Publication:Environmental Health Perspectives
Date:Dec 1, 2002
Words:452
Previous Article:Profiles in cancer. (Molecular Biology).
Next Article:EHP Toxicogenomics. (ehpnet).



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