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Repair of DNA by Brca2 gene prevents medulloblastoma

Investigators at St. Jude Children's Research Hospital have gained some of the first major insights into how certain genes known to prevent cancer also guide the normal development of the nervous system before birth and during infancy by repairing DNA damage.

The St. Jude researchers demonstrated that the Brca2 gene plays a dual role in the developing nervous system, eliminating errors in the DNA of newly made copies of chromosomes and suppressing the onset of the brain cancer medulloblastoma. Medulloblastoma is a cancer of the cerebellumthe lower back part of the brain that controls complex motor functions and communicates with other parts of the brain. This cancer accounts for about 20 percent of childhood brain tumors, about half of which occur in children younger than six years.

The role of Brca2 is important because as the cerebellum grows in size and complexity before and shortly after birth, it rapidly produces many new nerve cells.

"Our study showed that the Brca2 gene acts as a surveillance mechanism that triggers repair of DNA that is damaged when the cell makes a duplicate set of its chromosomes each time it divides," said Peter McKinnon, Ph.D., associate member of the Genetics and Tumor Cell Biology department at St. Jude. "The enormous rate of cell divisions during growth of the cerebellum greatly increases the risk of DNA damage. So the cell must have a way to ensure that the damage is quickly repaired to prevent the accumulation of abnormal cells that can cause abnormalities, such as medulloblastoma." McKinnon is senior author of a report on this work in the advanced online version of "The EMBO Journal" (doi: 10.1038/sj.emboj.7601703).

When researchers eliminated Brca2 from the developing nervous system in mice, the loss of this gene led to widespread apoptosis, or cell suicide, triggered by the cells inability to repair DNA damage. This reduced the size of the cerebellum, led to malformation in the shape
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Contact: Summer Freeman
summer.freeman@stjude.org
901-495-3061
St. Jude Children's Research Hospital
18-May-2007


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