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Biologists at Tufts University discover 1 reason why chromosomes break, often leading to cancer

MEDFORD/SOMERVILLE, Mass. In the past ten years, researchers in genome stability have observed that many kinds of cancer are associated with areas where human chromosomes break. They have hypothesized but never proven that slow or altered replication led to the chromosomes breaking.

In a Tufts University study published in the Aug. 3 journal "Molecular Cell," two molecular biologists have used yeast artificial chromosomes to prove the hypothesis. The Tufts researchers have found a highly flexible DNA sequence that increases fragility and stalls replication, which then causes the chromosome to break.

Catherine Freudenreich, associate professor of biology at the School of Arts and Sciences at Tufts University, and doctoral student Haihua Zhang focused on one particular human common fragile site an area that is a normal part of chromosome structure but is prone to breaking. The site lies in the middle of a tumor suppressor gene and chromosome breakage in this area is highly associated with cancer.

"It is an area that has a tumor suppressor gene a gene whose absence can cause tumors," explained Freudenreich. "If you delete that gene or delete part of that gene so it doesn't work anymore, that can lead to tumors. The fact that there is fragility in the same region that this gene is located is a bad coincidence."

"Fragility can cause deletions and deletions can cause cancer, so you want to understand the fragility because that might be what's causing cancer," she continued.

DNA structure leads to fragility

Past research had predicted the flexibility of the DNA helix in this particular common fragile site by calculating the twist angle between consecutive base pairs and found that there were several points of high flexibility, suggesting that the flexibility was connected to the fragility.

Freudenreich and Zhang used yeast artificial chromosomes to test this idea because it allowed them t
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Contact: Suzanne Miller
suzanne_c.miller@tufts.edu
617-627-4703
Tufts University
2-Aug-2007


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