Analysis of the genome reveals that DNA sequences prone to forming the Z-DNA structure occur in 0.25 percent of the genome, according to Vasquez.
She and her colleagues decided to find out whether Z-DNA itself had any effect on the DNA stability. To do that, post-doctoral fellow Guliang Wang, Ph.D., made pieces of DNA designed to form the Z-DNA shape.
The researchers then introduced these segments of DNA, called plasmids, into bacterial cells and human cells in the laboratory. They then broke apart the cells and examined what happens to the DNA. They found that in bacterial cells, the Z-DNA caused small deletions or insertions of one or two DNA bases. But in human cells, the introduced Z-DNA led to large-scale deletions and rearrangements of the DNA molecule.
"We discovered that bacterial cells and human cells process the Z-DNA in different ways," she says. "We aren't sure why, but we think that the DNA repair machinery may be involved in processing the Z-DNA structure differently in bacteria versus human cells."
Since formation of Z-DNA is naturally occurring and can exist in the genome, the scientists next want to understand why cells can sometimes process the structure without creating double-stranded breaks.
They also want to know why certain places in the genome become "hot spots" for these breaks, while other seemingly similar areas do not.
"If we could understand the players involved in this process, we might be able to prevent the generation of these breaks," says Vasquez. "For example, if certain types of cell stress lead to breaks, we might be able to find ways to red
Contact: Nancy Jensen
University of Texas M. D. Anderson Cancer Center