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Researchers identify gene as protector of DNA, enemy of tumors

Houston -- A single gene plays a pivotal role launching two DNA damage detection and repair pathways in the human genome, suggesting that it functions as a previously unidentified tumor suppressor gene, researchers at The University of Texas M. D. Anderson Cancer Center report in Cancer Cell.

The advance online publication also reports that the gene - called BRIT1 - is under-expressed in human ovarian, breast and prostate cancer cell lines.

Defects in BRIT1 seem to be a key pathological alteration in cancer initiation and progression, the authors note, and further understanding of its function may contribute to novel, therapeutic approaches to cancer.

"Disruption of BRIT1 function abolishes DNA damage responses and leads to genomic instability," said senior author Shiaw-Yih Lin, Ph.D., assistant professor in the Department of Molecular Therapeutics at M. D. Anderson. Genomic instability fuels the initiation, growth and spread of cancer.

A signaling network of molecular checkpoint pathways protects the human genome by detecting DNA damage, initiating repair and halting division of the damaged cell so that it does not replicate.

In a series of laboratory experiments, Lin and colleagues show that BRIT1 activates two of these checkpoint pathways. The ATM pathway springs into action in response to damage caused by ionizing radiation. The ATR pathway responds to DNA damage caused by ultraviolet radiation.

By using small interfering RNA (siRNA) to silence the BRIT1 gene, the scientists shut down both checkpoint pathways in cells exposed to either type of radiation.

Researchers then used siRNA to silence the gene in normal human mammary epithelial cells (HMEC). The result: Inactivation of the gene caused chromosomal aberrations in 21.2 to 25.6 percent of cells. Control group HMEC had no cells with chromosomal aberrations. In cells with the gene silenced that were then exposed to ionizing radiation, 80
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Contact: Scott Merville
sdmervil@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
3-Aug-2006


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