To their surprise, immunologists discovered two decades ago that breaking DNA was the source of one of the immune system's great strengths. Human DNA contains only 30,000 human genes, but the immune system makes proteins known as antibodies that recognize billions of different foreign substances. Immunologists showed that this was because lymphocytes create double-strand DNA breaks that allowed them to splice together their genetic materials in new ways. Material created from the new genetic combinations is used to generate antibodies and other defensive mechanisms that help the body defend itself against a much greater variety of invaders.
Sleckman wanted to examine the implications of DNA breaks in lymphocytes. In a cell line developed in his lab, researchers induced double-stranded breaks in lymphocyte DNA using the same enzymes the cells normally use to create the breaks. They then analyzed the genes activated as a result.
As expected, the breaks turned on two groups of genes: one, headed by the p53 protein, pushes the cell toward self-destruction; the other, headed by the NFKappa-B proteins, pushes for survival of the cell and repair of the damaged DNA. These groups of genes are normally activated in any cell that experiences DNA damage.
But Sleckman and his colleagues also found several lymphocyte-specific genes activated by the breaks.
"Several of these genes are involved in the migration and homing of lymphocytes," says Sleckman. "Lymphocytes are made in the bone marrow and the thymus, and they have to move to other niches, including the lymph glands, to do their work."
In addition to the young lymphocyte, scientists are aware of other instances where DNA is normally and regularly broken, such as the
|Contact: Michael C. Purdy|
Washington University School of Medicine