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Molecular Nano-Motor to Repair Damage in DNA Structure

Researchers at The Scripps Research Institute have developed a technology that offers insights into the functioning of the molecular motor inside the DNA structure. This development, they say could impact treatment of medical problems ranging from cancer to cystic fibrosis.

The research paper has been published in an Advance Online Edition of Nature Structural and Molecular Biology dated March 27. The motor molecule Rad50 is a flexible protein whose shape changes and rotates depending on what is required of it. The discovery describes how an individual protein structure MRN (Mre11-Rad50-Nbs1) can mend DNA in multiple tricky ways, according to team leaders Scripps Research Professor John Tainer and Scripps Research Professor Paul Russell who also worked with a team from the Lawrence Berkeley National Laboratory on the study.

The discovery offers an insight into the ABC-ATPase superfamily of molecular motors. Understanding the functioning of the Rad50 and related proteins in this family will provide insights into how to control biological outcomes. Rad50 changes its shape according to the task at hand, suggesting it could target elements in that particular conformation. Russell says that their work has revealed moving parts in the DNA protein structure. They move and alter shape when working with other molecules.

The MRN is a first-responder molecule that runs to mend double-strand breaks in the DNA helix to avoid chromosomal rearrangements that cause cancer. It also repairs breaks caused by chemotherapy.

Working with the team at the Berkeley Laboratory and its Advanced Light Source beam line called SIBYLS, a series of high-resolution pictures of the crystal structure of the three proteins (rad50, Mre11, and Nbs1) from fission yeast and archaea, the proteins' overall structure in solution was determined, which reveals the appearance of a protein in a natural state.

Source: http://www.scripps.edu/

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