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The Dual Role Of BRCA2 In DNA Repair

 
  May, 31 2007 8:53
your information resource in human molecular genetics
 
     
The dual role of the gene BRCA2 in DNA repair is described in two independent studies in the June 2007 issue of Nature Structural & Molecular Biology. The studies from Stephen West's and Luca Pellegrini's groups shed light on the role of the gene, mutations of which result in predisposition to breast cancer and other malignancies.

The protein encoded by BRCA2 is involved in homologous recombination, a process whereby damaged DNA is repaired using an intact copy of DNA as a template. This process also includes the protein RAD51, which interacts directly with two different regions of BRCA2, called BRC and TR2. The BRC region had been previously suggested to be involved in terminating homologous recombination. Data from the two present studies indicate that the TR2 region can oppose the activity of BRC, suggesting that BRCA2 contains regions that both favor and disrupt homologous recombination. These activities might operate at different stages of DNA repair.

Both reports also provide insight into how the opposing activities of BRCA2 can be regulated -- a phosphorylation event at TR2 results in the loss of its interaction with RAD51, acting as a turn-off switch. These findings advance our knowledge of BRCA2's role in genetic stability, and contribute to our understanding of why mutations in BRCA2 increase the likelihood of cancer.

Author contacts:

Stephen West (Cancer Research UK, London, United Kingdom)
E-mail: stephen.west@cancer.org.uk

Luca Pellegrini (University of Cambridge, United Kingdom)
E-mail: luca@cryst.bioc.cam.ac.uk

Abstracts available online:
West Paper.
Pellegrini Paper.

(C) Nature Structural & Molecular Biology press release.


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