Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers probe a DNA repair enzyme

19.02.2008
U. of I. 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.

... more about:
»Cluster »DNA »Domain »Rad3 »enzyme »helicase

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 cell’s 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 it’s 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.”

This research was performed in collaboration with Isaac Caan’s group from Animal Sciences whose lab is engaged in the study of nucleotide metabolism in archaea.

Editor’s note: To reach Maria Spies, call 217-244-9493; e-mail: mspies@life.uiuc.edu

Kaushik Ragunathan | University of Illinois
Further information:
http://www.news.uiuc.edu/news/08/0218helicase.html

Further reports about: Cluster DNA Domain Rad3 enzyme helicase

More articles from Life Sciences:

nachricht Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz

nachricht Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>