Navigation Links
Researchers probe a DNA repair enzyme
Date:2/18/2008

Researchers have taken the first steps toward understanding how an enzyme repairs DNA.

Enzymes called helicases play a key role in human health, according to Maria Spies, a University of Illinois biochemistry professor.

DNA helicases act as critical components in many molecular machineries orchestrating DNA repair in the cell. she said. Multiple diseases including cancer and aging are associated with malfunctions in these enzymes.

Spies laboratory undertook a recent study of an enzyme, called Rad3, which defines a group of DNA helicases characterized by a unique structural domain containing iron. The findings appear in the Journal of Biological Chemistry.

Helicases are a special category of molecular motors that modify DNA (deoxyribonucleic acid, the fundamental building block of genes and chromosomes). They do so by moving along strands of DNA, much the same way cars move on roads, using an energy-packed molecule, adenosine triphosphate (ATP) as a fuel source.

Their primary function is to unzip double-stranded DNA, allowing replication and repair of the strands.

DNA is a fragile molecule that undergoes dramatic changes when exposed to radiation, ultraviolet light, toxic chemicals or byproducts of normal cellular processes. DNA damage, if not repaired in time, may lead to mutations, cancer or cell death. Many helicases in the Rad3 family are key players in the cells elaborate machinery to prevent and repair such damage. Mutations in the human members of this helicase family impede DNA repair and may contribute to breast cancer, Fanconi Anemia and Xeroderma pigmentosum.

The researchers studied the archaeal version of Rad3. Archaea are microbes whose DNA repair systems are closely related to those of human cells.

(The archaeal Rad3) is a very good representative of a unique family of structurally related DNA repair helicases, all of which have the same motor core and share an unprecedented (for helicases) structural feature an accessory domain stabilized by an iron-sulfur cluster, Spies said.

Working with archaea has the advantage of allowing the researchers to increase the amount available protein and also permits easy genetic manipulation.

Like other helicases, Rad3 is composed of a chain of amino acids. It also contains an ancient prosthetic group called an iron-sulfur cluster, an assembly of four iron and four sulfur atoms incorporated into the protein structure through interaction with four cysteine residues of the amino acid chain.

"DNA helicases, which belong to the Rad3 family, have an auxiliary domain inserted within a conserved motor core. The structure of this domain is stabilized by an iron-sulfur cluster, whose integrity seems to be essential for proper function of these enzymes in DNA repair," Spies said. By mutating the cysteine ligands to the cluster, the researchers probed its role in the molecular mechanism of Rad3 enzymes. Some of these mutations uncoupled DNA translocation and ATP hydrolysis, meaning that the engine of the protein could still use the ATP fuel but was no longer capable of moving along the DNA.

This analysis also revealed that the integrity of the cluster and the iron-containing domain is crucial for recognition of specific DNA structures believed to be physiological targets for this helicase. On making these mutations, the helicase no longer behaves like its supposed to, said graduate student Robert Pugh, lead author on the study. The cluster is still there but the environment around it is somehow changing.


'/>"/>

Contact: Diana Yates
diya@uiuc.edu
217-333-5802
University of Illinois at Urbana-Champaign
Source:Eurekalert  

Related biology news :

1. Oregon researchers study widespread areas of low oxygen off northwest coast
2. Stanford researchers say living corals thousands of years old hold clues to past climate changes
3. Stanford researchers make first direct observation of 3-D molecule folding in real time
4. Dartmouth researchers find the root of the evolutionary emergence of vertebrates
5. Researchers decode genetics of rare photosynthetic bacterium
6. Researchers decode genetics of rare photosynthetic bacteria
7. Stevens researchers provide oversight for three-year mariculture program in Egypt and Israel
8. Hot springs microbes hold key to dating sedimentary rocks, researchers say
9. Stem-cell transplantation improves muscles in MD animal model, UT Southwestern researchers report
10. Tiny genetic differences have huge consequences: McGill researchers
11. MNI researchers locate neurological basis of depression following sports concussion
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Researchers probe a DNA repair enzyme
(Date:2/3/2016)... Vigilant Solutions announces today that the ... Missouri solved two recent hit-and-run cases with ... Vigilant Solutions. Brian Wenberg explains, "I ... was walking out of a convenience store and witnessed an elderly male back ... striking his vehicle and leaving the scene.  In his ...
(Date:2/2/2016)... , Feb. 2, 2016 This BCC ... bioinformatic market by reviewing the recent advances in ... that drive the field forward. Includes forecast through ... Identify the challenges and opportunities that exist in ... software solution developers, as well as IT and ...
(Date:2/2/2016)... 2016   Parabon NanoLabs (Parabon) announced ... Research Office and the Defense Forensics and Biometrics ... the company,s Snapshot Kinship Inference software ... generally, defense-related DNA forensics.  Although Snapshot is best ... and ancestry from DNA evidence), it also has ...
Breaking Biology News(10 mins):
(Date:2/10/2016)... ... 2016 , ... Cenna Bioscience Inc., an emerging biopharmaceutical company focused on the ... it has been selected to present at the Cavendish Global Health Impact Forum taking ... The purpose of the Forum is to help family offices and foundations develop and ...
(Date:2/9/2016)... , ... February 09, 2016 , ... With a presidential ... Wharton Health Care Business Conference will bring together over 500 top healthcare leaders for ... industry in transformation. The conference, organized by MBA students of the University of Pennsylvania’s ...
(Date:2/9/2016)... , ... February 08, 2016 , ... ... , Location: Baruch S. Blumberg Institute at the Pennsylvania Biotechnology Center of Bucks ... Institute and The Commonwealth Medical College (TCMC) will hold an open house for ...
(Date:2/9/2016)... CA (PRWEB) , ... February 09, 2016 , ... ... present its latest innovations on its free and validated Electronic Data Capture (EDC) ... #81 the Outsourcing in Clinical Trials West Coast 2016 Conference in San Mateo, ...
Breaking Biology Technology: