Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Unusual mechanism keeps repair protein accurate

26.07.2006
Cancer researchers have discovered that a recently identified protein critical for repairing damaged genes uses an unusual mechanism to keep its repairs accurate.

The protein, called DNA polymerase lambda, is one of a group of proteins known as DNA polymerases that are vital for accurately making and repairing DNA.

But while other DNA-repair proteins insure their accuracy with the help of so-called proof-reading regions or accessory molecules, this protein maintains its accuracy using an otherwise ordinary-looking portion of its molecular structure.

The study was led by Zucai Suo, assistant professor of biochemistry and a researcher with the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute. The research, published in the July 14 issue of The Journal of Biological Chemistry, provides new insights into how cells repair damaged DNA.

“DNA is constantly attacked and damaged by a variety of agents,” Suo says. “The body must properly repair that damage, or it can lead to cell death or to cancer, birth defects and other diseases.

“There are six families of DNA polymerases,” Suo says, “and this is the first polymerase to use this mechanism to maintain its accuracy when making new DNA. It is both surprising and unprecedented.”

The repair protein itself was first discovered by scientists studying DNA sequence data produced by the Human Genome Project. Suo and his colleagues then became interested in learning how the repair protein worked.

The protein has four distinct regions, or domains. Three of the regions had molecular structures that strongly suggest the task they performed.

For example, regions three and four closely resemble a well-known repair protein called DNA polymerase beta. In fact, it was this similarity that tipped off scientists that the new protein was probably involved in DNA repair.

Region one also had a predicted structure that should allow it to “dock” with other proteins. “This suggests that this protein may do more than just fix DNA damage,” Suo says.

Region two held the surprise. It is called the proline-rich domain because it has high levels of the amino acid proline.

“There was no known function for a structure like the proline-rich domain, so we at first thought it did nothing more than connect the docking region of the protein with regions three and four,” Suo says.

“Then by accident we learned that this was not just a structural connection, but that it is critical to the protein's ability to replicate DNA with very few mistakes.”

For this study, Suo and his colleagues wanted to learn how efficiently the new protein made new DNA. But the researchers initially considered the protein too large and difficult to produce in the laboratory. So instead of making the entire protein, the researchers made only the part that does the repair work, regions three and four.

When they tested this short version of the protein, however, they found that it made up to a 100 times more mistakes than did the similar repair protein, DNA polymerase beta.

“That error rate is too high,” Suo says. “If the entire repair protein produced that many errors, it would cause more problems than it would fix.”

Next, the researchers made the entire protein and found that it could repair DNA as accurately as the comparison protein.

Last, they tested a version of the protein that lacked the docking region. This shortened molecule also accurately made DNA.

“To find that the proline-rich domain was responsible for this repair protein's high fidelity came as a complete surprise,” Suo says.

Presently the scientists are studying the three-dimensional structure of the entire protein to learn how the presence of a proline-rich region influences the ability of the protein to accurately make DNA.

Funding from the National Institutes of Health Chemistry and Biology Interface Program and from the American Heart Association Predoctoral Fellowship program supported this research.

Darrell E. Ward | EurekAlert!
Further information:
http://www.osu.edu

More articles from Life Sciences:

nachricht Topologische Quantenchemie
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

nachricht Topological Quantum Chemistry
21.07.2017 | Max-Planck-Institut für Chemische Physik fester Stoffe

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: 3-D scanning with water

3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects

A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

 
Latest News

Ultrathin device harvests electricity from human motion

24.07.2017 | Power and Electrical Engineering

Scientists announce the quest for high-index materials

24.07.2017 | Materials Sciences

ADIR Project: Lasers Recover Valuable Materials

24.07.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>