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Jonsson巨蟹星座中心研究员开发测试确定素质对巨蟹星座

Joan Trombetti, Writer | March 25, 2009
Jonsson Cancer Center
A study by researchers at UCLA's Jonsson Cancer Center may help identify new genes that can predict a predisposition to cancer. Published in the April issue of Radiation Research, the study was done in yeast and mammalian cells. The cancer cells showed persistent genetic instability and the researchers, led by Robert Schiestl, discovered a mechanism that switches on that genetic instability. If they can uncover and understand the molecular pathways at work in promoting genetic instability, they may be able to develop ways to switch that mechanism off, restoring stability.

The assay determines the efficiency of the repair mechanism when DNA suffers a double-strand break, when both strands in the double helix are severed. These breaks cause genetic instability and are particularly dangerous because they can lead to genome rearrangements or deletions of certain genes that, when gone, result in cancer; a cell that can't efficiently repair itself could result in cancer.

In the study, researchers irradiated cells to create double strand breaks. They wanted to determine if a double strand break occurs in one area of the DNA is the instability limited to that area or also evident elsewhere. The standard thinking was that the genetic instability would be localized to the area of the break. However, Schiestl and his team showed that a break in one area has an "in trans" effect, meaning the instability could surface anywhere.

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The research team irradiated cells and then transformed them with a DNA fragment that detects the efficiency and the accuracy of double strand break repair. The key in this experiment was that the DNA fragment was not irradiated. In this way, the researchers could demonstrate that the radiation triggered a specific mechanism of double strand break repair in the DNA fragment that did not receive any radiation. The effect was still noticeable after almost all the DNA damage the radiation caused in the cells was repaired, showing that the mechanism that is induced by the radiation is independent of the actual damage caused by the radiation.

Schiestl had previously shown that a single DNA double strand break also induces genetic instability all over the genome at sites that are not damaged, again a proof that double strand breaks induce genetic instability in trans.

Interestingly, many cancer cells show an elevated induction of the specific DNA double strand break repair mechanism found induced in trans in this study, as if the cancer cells had this mechanism somehow induced and were not able to switch it off.

The research was funded in part by a National Institutes of Health grant and a NASA graduate student fellowship. Other members of Schiestl's team included Zorica Scuric, Cecilia Chan and Kurt Hafer.

UCLA's Jonsson Comprehensive Cancer Center has more than 350 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation's largest comprehensive cancer centers, the Jonsson center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2008, the Jonsson Cancer Center was named among the top 10 cancer centers nationwide by U.S. News & World Report, a ranking it has held for nine consecutive years. For more information on the Jonsson Cancer Center, visit http://www.cancer.ucla.edu.