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Structure of DNA repair complex reveals workings of powerful cell motor
Date:3/27/2011

s complex. They are dynamic. They move about and change shape when engaging with other molecules."

First Responder

The MRN complex is known as a first-responder molecule that rushes in to repair serious double-strand breaks in the DNA helixan event that normally occurs about 10 times a day per cell due to ultraviolet light and radiation damage, etc. If these breaks are not fixed, dangerous chromosomal rearrangements can occur that lead to cancer. Paradoxically, the complex also mends DNA breaks promoted by chemotherapy, protecting cells against cancer treatment.

When MRN senses a break, it activates an alarm telling the cell to shut down division until repairs are made. Then, it binds to ATP (an energy source) and repairs DNA in three different ways, depending on whether two ends of strands need to be joined together or if DNA sequences need to be replicated. "The same complex has to decide the extent of damage and be able to do multiple things," Tainer said. "The mystery was how it can do it all."

To find out, Tainer, head of a structural biology group, and Russell, who leads a yeast genetics laboratory, began collaborating five years ago. With the additional help of team members at Lawrence Berkeley National Laboratory and its Advanced Light Source beamline, called SIBYLS, the collaboration has produced a series of high-resolution images of the crystal structure of parts of all three proteins (rad50, Mre11, and Nbs1), taken from fission yeast and archaea. The scientists also used the lab's X-ray scattering tool to determine the proteins' overall architecture in solution, which approximates how a protein appears in a natural state.

The scientists say that the parts of the complex, when imagined together as a whole unit, resemble an octopus: the head consists of the repair machinery (the Rad50 motor and the Mre11 protein, which is an enzyme that can break bonds between nucleic acids) and the octopus arms are made u
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Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert

Page: 1 2 3 4

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