Navigation Links
Unusual mechanism keeps repair protein accurate

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 als o 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.


'"/>

Source:Ohio State University


Related biology news :

1. Unusual antibiotics show promise against deadly superbugs
2. A new mechanism of regulating RNA degradation
3. Plants, animals share molecular growth mechanisms
4. PET/MRI scans may help unravel mechanisms of prenatal drug damage
5. Researchers discover molecular mechanism that desensitizes us to cold
6. Chemists identify immune system mechanism for methamphetamine binges
7. Key mechanism in genetic inheritance during cell division identified
8. Researchers unlock mechanism creating jigsaw puzzle-like plant cells
9. Mouse gene shows new mechanism behind cardiac infarction in man
10. UCSD research reveals mechanism involved with type of fatal epilepsy
11. Ancient immune defense mechanism is no match for HIV-1
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:10/4/2017)...  GCE Solutions, a global clinical research organization (CRO), announces the ... on October 4, 2017. Shadow is designed to assist medical writers ... 0070 of the European Medicines Agency (EMA) in meeting the requirements ... ... ...
(Date:6/30/2017)... , June 30, 2017 Today, ... developer and supplier of face and eye tracking ... Featured Product provider program. "Artificial ... innovative way to monitor a driver,s attentiveness levels ... from being able to detect fatigue and prevent ...
(Date:5/16/2017)... May 16, 2017  Veratad Technologies, LLC ( www.veratad.com ... age and identity verification solutions, announced today they will ... 2017, May 15 thru May 17, 2017, in ... International Trade Center. Identity impacts the ... in today,s quickly evolving digital world, defining identity is ...
Breaking Biology News(10 mins):
(Date:10/12/2017)... ... October 12, 2017 , ... The Blavatnik Family ... and six Finalists of the 2017 Blavatnik Regional Awards for Young Scientists. ... and administered by the New York Academy of Sciences to honor the excellence ...
(Date:10/12/2017)... ... October 12, 2017 , ... AMRI, ... and biotechnology industries to improve patient outcomes and quality of life, will now ... testing are being attributed to new regulatory requirements for all new drug products, ...
(Date:10/11/2017)... ... ... a basic first aid supply for any work environment, but most personal eye wash can ... a dangerous substance enters both eyes? It’s one less decision, and likely quicker response time ... , “Whether its dirt and debris, or an acid or alkali, getting anything in your ...
(Date:10/11/2017)... the Netherlands and LAGUNA HILLS, Calif. ... The Institute of Cancer Research, London ... use MMprofiler™ with SKY92, SkylineDx,s prognostic tool to risk-stratify patients ... trial known as MUK nine . The University of ... trial, which is partly funded by Myeloma UK, and ICR ...
Breaking Biology Technology: