Chromosomes Born of Broken DNA

We inherit our genes thanks partly to DNA "handles" called centromeres that help a cell gently pry apart pairs of chromosomes, allowing them to be passed on to a daughter cell. Now scientists for the first time have witnessed a fragment from a damaged chromosome somehow sprout a centromere and get copied. The findings, reported in this month's Nature Genetics, might someday help researchers get a handle of their own on aberrant chromosome diseases and to make artificial chromosomes stacked with healthy genes for treating diseases such as cystic fibrosis.

In their efforts to pinpoint the positions of centromeres on fruit fly chromosomes, a team led by Gary Karpen of the Salk Institute in La Jolla, California, blasted flies with gamma rays, which broke the ends off of some of the chromosomes. Curiously, as the fruit fly cells divided, some of these chromosome fragments were passed down through dozens of generations to daughter cells.

Karpen's group suspected that a new centromere had formed on the fragments, allowing them to be pulled apart and copied. To test this idea, they showed that the new chromosomes would stick to a fluorescent antibody that binds to proteins that attach only to centromeres. Karpen argues that the gamma rays somehow transformed part of the original chromosome's DNA to a form that can develop a centromere. He speculates that before the chromosome's end broke off, the radiation first caused an DNA inversion, bringing the end near the centromere-forming regions. Karpen speculates that the centromere either added a protein or altered the structure of the chromosome end, thereby giving it the ability to become a centromere.

"It is tremendously thought-provoking," says Huntington Willard, a geneticist at Case Western Reserve University's School of Medicine. "A sequence that shouldn't have any idea how to be a centromere has been taught to adopt that role." If geneticists can learn how to turn any DNA into a centromere, that may help gene therapy researchers, who are currently trying to build artificial chromosomes that can deliver curative genes to patients with a genetic disease, Willard says.