Researchers Identify Protein That Detects Damaged DNA

Physicians have long marveled at the body’s ability to heal itself. Over time, breaks, tears, burns and bruises can often disappear sans medical intervention. Less well-understood are the similarly extraordinary repairs that take place on the molecular level, in DNA. To that end, findings announced today in the Proceedings of the National Academy of Sciences, may prove insightful. According to the report, researchers have found that a protein known as ATR appears to sense damage to DNA and touch off a sequence of events leading to molecular mending.

Ultraviolet radiation, chemotherapy and other agents can cause lesions in cellular DNA that must be fixed before the cell divides and replicates the mutations, which can lead to cancer, among other problems. Previous work had implicated ATR in the repair of damaged DNA, but exactly which part of that cascade of events the protein is responsible for remained a mystery. The new research, conducted by Aziz Sancar and his colleagues at the University of North Carolina, suggests that ATR directly detects DNA lesions and sounds the alarm bell, summoning the other members of the repair crew to duty, so to speak. “To find out if ATR directly sensed damaged DNA, we put a molecular tag on the ATR protein and purified it,” Sancar explains. “We incubated the tagged protein with either bits of DNA that were normal or damaged by UV radiation. ATR bound more often to damaged DNA than to undamaged DNA.” Furthermore, he notes, ATR’s activity increased when it encountered problematic DNA.

The results imply that ATR functions as an initial sensor in what is known as the DNA damage checkpoint response. “This is a very important phenomenon in both normal and cancerous cells,” Sancar observes. “ATR appears to act as a switch that starts the repair process and also stops cells from proliferating while they are being repaired.” Although the new work “is not going to cure cancer by itself,” he remarks, “it is a significant step forward” in that it could point the way to new anticancer drugs.