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Penn researchers identify new protein important in breast cancer gene's role in DNA repair
Date:3/18/2009

PHILADELPHIA -- For years, researchers have known that under normal conditions, the breast cancer protein BRCA1 orchestrates the repair of damaged DNA, but the details of just how BRCA1 moves to the damaged site and recruits the right nuclear repairmen for DNA restoration remains a mystery.

Now, a new study from the University of Pennsylvania School of Medicine has identified genes associated with the BRCA1 protein and their involvement in the DNA repair pathway, helping to clear the way for researchers to better understand what goes wrong when the BRCA1 gene is mutated and the repair pathway goes haywire. Identifying patients with mutations in these BRCA1-associated genes may help better fight breast cancer.

The new study appears in the most recent issue of Genes & Development.

"A mutated BRCA1 gene increases vulnerability to breast and ovarian cancers by increasing the rate at which genes are altered," says Roger Greenberg, MD, PhD, Assistant Professor of Cancer Biology at the Abramson Family Cancer Research Institute at the University of Pennsylvania. Previous studies have shown that mutated BRCA1-associated proteins also increase the risk of breast cancer, implying that a BRCA1-centered DNA repair pathway is necessary to suppress cancer.

About two years ago, Greenberg helped to lead a study that identified the role of a BRCA1-associated protein called RAP80. The BRCA1 protein works in partnership with RAP80 to locate damaged DNA sites. Cancer-causing mutant BRCA1 proteins fail to pair up with RAP80, which, in turn, blinds BRCA1 to DNA damage. The results of the study led Greenberg's group to look closer at the interaction between BRCA1 and RAP80 to learn the molecular details of how this complex functioned in DNA repair and to explore RAP80 as a possible breast-cancer-susceptibility gene candidate.

In the latest study, Greenberg's team returned to the BRCA1-RAP80 complex for additional analysis, and ident
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

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