St. Louis, Oct.20, 2008 Researchers have shown that self-induced breaks in the DNA of immune cells known as lymphocytes activate genes that cause the cells to travel from where they're made to where they help the body fight invaders.
Scientists have known for two decades or more that lymphocytes can break their own DNA in this fashion, creating splits in both of the two strands. However, the new finding is the first to link such serious damage to activation of genes not directly involved in the cells' attempts to either fix the harm or self-destruct to stop themselves from becoming cancerous.
When genes are activated is critical to the ability of cells to take on specialized roles in the body, and the finding, published online in Nature, left researchers wondering if other developmental pathways in different cell types are also triggered by DNA damage.
"It's also interesting to note that the cell sees the genetic material of some invaders, such as DNA viruses, as damaged DNA," says senior author Barry Sleckman, M.D., Ph.D, director of the Division of Laboratory and Genomic Medicine and an expert in DNA repair. "Could pathogens be taking advantage of these pathways outside of the previously recognized responses to DNA damage? We don't know yet."
The finding immediately improved scientists' understanding of ataxia telangiectasia, a rare genetic disorder that, among other symptoms, can weaken the immune system. Patients with the disorder have a mutation in a gene, ATM, that normally helps the cell sense DNA damage.
"This explains why the lymphocyte counts in these patients drop so sharply," Sleckman says. "Not only is the cell's ability to repair DNA damage slowed down, the lymphocytes can't activate the genes that get them to where they need to be."
Cells have built-in safeguards that regularly look for DNA damage. They can then repair it, or if that's not possible, push the cell to self-destruct. B
|Contact: Michael C. Purdy|
Washington University School of Medicine