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When good DNA goes bad

When otherwise normal DNA adopts an unusual shape called Z-DNA, it can lead to the kind of genetic instability associated with cancers such as leukemia and lymphoma, according to a study by researchers at The University of Texas M. D. Anderson Cancer Center.

The study, issued in advance of the Feb. 21 edition of the Proceedings of the National Academy of Sciences, demonstrates for the first time that the oddly shaped DNA can cause DNA breaks in mammalian cells.

Interestingly, these sequences prone to forming Z-DNA are often found in genetic "hot spots," areas of DNA known to be prone to the genetic rearrangements associated with cancer. About 90 percent of patients with Burkitt's lymphoma, for example, have DNA breaks that map to regions with the potential to form these odd DNA structures.

"Our study shows that DNA itself can act as a mutagen, resulting in genetic instability," says Karen Vasquez, Ph.D., lead author of the study and assistant professor of carcinogenesis at M. D. Anderson's Science Park Research Division, Smithville, Texas. "The discovery opens up a new field of inquiry into the role of DNA shape in genomic instability and cancer."

Imagine untwisting the DNA ladder and then winding it up the other way. The result is a twisted mess with segments jutting out left and right, and the all important base pairs that hold the DNA code zigzagging in a jagged zipper shape. Scientists call this left-hand twist Z-DNA. This is a far cry from the graceful right-hand twisted helix that has become an iconic symbol of biology. It just doesn't look right, and it doesn't act right either, according to Vasquez. This awkward shape puts strain on the DNA, and as Vasquez and her colleagues show, can cause the DNA molecule to break completely apart.

Scientists have known for many years that DNA can take shapes other than the typical twisted ladder form, but they weren't sure how often these alternate shapes occur inside cells. Resear
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Source:University of Texas M. D. Anderson Cancer Center


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