Memorial Sloan-Kettering scientists uncover function of BRCA2 protein

NEW YORK, September 13, 2002 -- Structural biologists at Memorial Sloan-Kettering Cancer Center (MSKCC) have discovered the function of the protein BRCA2. Mutations in the BRCA2 gene have been linked to hereditary breast and ovarian cancers. The results were reported in the September 13 issue of Science.

BRCA2 was already known to be a tumor suppressor -- a protective protein that prevents the development of cancer -- but exactly how the protein does its job was not understood. Now MSKCC scientists have been able to map out the structure of the protein, showing that it interacts directly with DNA and helps to repair genetic damage. An inability to correct genetic damage leads to unstable chromosomes and often to cancer.

"If BRCA2 is altered or missing, it leads to a dangerous accumulation of genetic errors," said the study's senior author Nikola P. Pavletich, PhD, head of MSKCC's Laboratory of Structural Biology of Oncogenes and Tumor Suppressors and an investigator in the Howard Hughes Medical Institute. "By studying the normal function of BRCA2, we can understand how changes in the protein contribute to the development of cancer."

BRCA2 is an unusually large molecule, which has made it difficult for researchers to study. But Dr. Pavletich's team, including first author Haijuan Yang, found a way around that problem and was able to crystallize the protein. Those crystals were then bombarded with high-energy X-rays, a process called X-ray crystallography, and the diffraction patterns created by the X-rays were used to calculate the three-dimensional picture of the protein. This picture revealed that BRCA2 is similar in structure to other proteins known to bind DNA. The researchers then took the work a step further, showing that BRCA2 does indeed bind to DNA in special regions that are commonly found around broken DNA strands.

Researchers showed that BRCA2 participates in the repair of "double-strand" breaks: These breaks are a particularl

Contact: Christine Hickey
Memorial Sloan-Kettering Cancer Center

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