The structure of the Mre11 protein bo...( BERKELEY CA Repairing breaks in the...)

BERKELEY, CA Repairing breaks in the two strands of the DNA double helix is critical for avoiding cancer. In humans and other organisms, a molecular machine called the MRN complex is responsible for finding and signaling double-strand breaks (DSBs), then launching the error-free method of DNA repair called homologous recombination.

In an article in the online October 3, 2008 issue of the journal Cell, John Tainer of the Life Sciences Division at the U.S. Department of Energy's Lawrence Berkeley National Laboratory, leading a team of his colleagues from the Scripps Research Institute, reveals how the central component of the MRN complex performs its essential functions.

The core of the MRN complex is the protein Mre11 (M stands for Mre11, R for the Rad50 protein, and N for the Nbs1 protein). But without good models of how Mre11 interacts with DNA, based on evidence from high-resolution images, it was impossible to know how Mre11 recognizes the ends of the broken DNA and how or even whether it remodels DNA sequences. So just how Mre11 works has been a matter of dispute. Tainer and his colleague resolved these issues by going beyond images of the stand-alone structure of Mre11 to study Mre11 bound to DNA during the first steps of DSB repair.

"This breakthrough was possible because combined project efforts, funded by DOE to characterize microbial complexes and by the National Cancer Institute to examine complexes relevant to cancer, came together to define these DNA complexes," says Tainer. "Understanding how the body responds to DNA damage is fundamental for many potential cancer interventions and gene therapies. These results are especially exciting, as they open the door to the predetermined control of homologous recombination for cancer therapeutics and gene targeting."

The power of homologous recombination

Homologous recombination is important not only for error-free repair of DSBs but also fo
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