Detector of DNA damage: Structure of a repair factor revealed

June 19, 2012

Double-stranded breaks in cellular DNA can trigger tumorigenesis. Researchers from Ludwig-Maximilians-Universitaet (LMU) in Munich, Germany, have determined the structure of a protein involved in the repair and signaling of DNA double-strand breaks. The work throws new light on the origins of neurodegenerative diseases and certain tumor types.

Agents such as radiation or can cause double-stranded breaks in genomic DNA, which facilitate the development of tumors or the neurodegenerative disorders ataxia telangiectasia (AT) and AT-like disease (ATLD). Hence efficient repair mechanisms are essential for and function. The so-called MRN complex is an important component of one such system, and its structure has just been elucidated by a team led by Professor Karl-Peter Hopfner of LMU's Gene Center.

The MRN complex consists of the nuclease Mre11, the ATPase Rad50 and the protein Nbs1. Nbs1 is responsible for recruiting the protein ATM, which plays a central role in early stages of the cellular response to , to the site of damage. "How the MRN complex actually recognizes double-stranded breaks is still not clear," says Hopfner. He and his colleagues therefore set out to clarify the issue by analyzing the structures of mutant, functionally defective versions of the complex.

"We found that pairs of Mre11 molecules form a flexible dimer, which is stabilized by Nbs1." Mutations in different subunits of the complex are associated with distinct syndromes, marked by a predisposition to certain cancers, sensitivity to radiation or neurodegeneration. Hopfner's results help to explain these differences. For instance, the mutation linked to ATLD lies within the zone of contact between Mre11 and Nbs1, and may inhibit activation of ATM by weakening their interaction.

Related Stories

Recommended for you

A sodium surprise: Engineers find unexpected result during cardiac research

July 20, 2017
Irregular heartbeat—or arrhythmia—can have sudden and often fatal consequences. A biomedical engineering team at Washington University in St. Louis examining molecular behavior in cardiac tissue recently made a surprising ...

Want to win at sports? Take a cue from these mighty mice

July 20, 2017
As student athletes hit training fields this summer to gain the competitive edge, a new study shows how the experiences of a tiny mouse can put them on the path to winning.

'Smart' robot technology could give stroke rehab a boost

July 19, 2017
Scientists say they have developed a "smart" robotic harness that might make it easier for people to learn to walk again after a stroke or spinal cord injury.

Engineered liver tissue expands after transplant

July 19, 2017
Many diseases, including cirrhosis and hepatitis, can lead to liver failure. More than 17,000 Americans suffering from these diseases are now waiting for liver transplants, but significantly fewer livers are available.

Lunatic Fringe gene plays key role in the renewable brain

July 19, 2017
The discovery that the brain can generate new cells - about 700 new neurons each day - has triggered investigations to uncover how this process is regulated. Researchers at Baylor College of Medicine and Jan and Dan Duncan ...

New animal models for hepatitis C could pave the way for a vaccine

July 19, 2017
They say that an ounce of prevention is worth a pound of cure. In the case of hepatitis C—a disease that affects nearly 71 million people worldwide, causing cirrhosis and liver cancer if left untreated—it might be worth ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.