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Scripps research scientists find missing puzzle piece of powerful DNA repair complex
Date:10/1/2009

LA JOLLA, CA September 30, 2009 Researchers at The Scripps Research Institute have found, crystallized, and biologically characterized a poorly defined component of a key molecular complex that helps people to avoid cancer, but that also helps cancer cells resist chemotherapy.

The research was published in the October 2, 2009 issue of the journal Cell.

This biological machinethe Mre11-Rad50-Nbs1 (MRN) complexsenses and repairs serious forms of DNA damage, the kind that occur when both strands of the DNA helix are severed. In the new study, the scientists show how the Nbs1 componentthe last major component of the complex to be describedacts like flexible arms on an octopus, reaching out and grabbing molecules needed to help in the active repair of these double-strand breaks.

Scientists believe such breaks (DNA double strand breaks, or DSBs) occur normally about 10 times a day per cell, due to normal DNA processes including replication as well as hazards such as sun exposure, etc. If these breaks are not fixed, dangerous chromosomal rearrangements occur that can lead to cancer.

"Major goals of cancer research over the past decade have been to identify the molecular underpinnings of cancer, and to provide the foundation for development of novel approaches to intervention," says Scripps Research Professor John Tainer, Ph.D., who led the research with Scripps Research Professor Paul Russell, Ph.D. "A major advance has been identification of the MRN complex as a critical suppressor of cancer development, and we now have the final piece of the picture of how cells fix a severe type of DNA damage that can lead to cancer."

But while the MRN complex is needed to keep a cell healthy, it can also unfortunately repair diseased cells that therapies are targeting for destruction. For example, a substantial proportion of chemotherapy treatments are designed to induce these double-strand breaks, which can then be repaired b
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Contact: Keith McKeown
kmckeown@scripps.edu
858-784-8134
Scripps Research Institute
Source:Eurekalert

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