Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Guardian of the genome: Structure of key enzyme decoded

05.07.2017

Scientists from the University of Würzburg solved the structure of the human protein RecQ4 and gained insights into its unusual functional mechanisms, which could help towards the development of new therapeutic strategies against certain tumors.

Living organisms aim to preserve their genomic integrity to maintain cellular functions and to pass on the correct genetic information to following generations. An important role in preserving genetic information is performed by RecQ helicases, a group of enzymes that is involved in central DNA-based processes, including DNA replication, recombination and repair. RecQ helicases are highly conserved among all living organisms, from bacteria to humans.


The structure of RecQ4 features the conserved helicase core domains (blue), which are connected to the novel RecQ4-zinc-binding domain (green) via a bridging helix bundle (grey). Zinc ion in turquoise

Photo: Kisker Group

In humans, malfunction of these important enzymes causes serious chromosomal damages, resulting in fatal diseases. The development of novel therapies to treat such diseases relies on the detailed knowledge of how these RecQ helicases operate at the molecular level.

RecQ4 is involved in cancer development

Scientists of the Rudolf Virchow Center for Experimental Biomedicine at the University of Würzburg investigated a particular member of this central enzyme family, called RecQ4. It is known that an impairment of RecQ4 function promotes the development of different types of cancer and provokes symptoms of premature aging. Moreover, mutations in the RecQ4 helicase are linked to systemic diseases like the Rothmund-Thomson-Syndrome and RAPADILINO-Syndrome, which are characterized by skeletal abnormalities and growth retardation.

Researchers from the group of Prof. Caroline Kisker now successfully determined the crystal structure of the human RecQ4 helicase and identified unique domains in this protein, which are not shared with any other RecQ member. While the helicase core comprises the conserved structural fold of a molecular power station that provides the energy to unwind the double-stranded DNA, further functional domains that are characteristic for the enzyme family are missing. Instead, the scientists identified a novel protein domain that is potentially responsible for specific RecQ4 functions.

An uncommon mechanism

Due to the special structural properties of RecQ4, the scientists assume an uncommon helicase mechanism. "Other human RecQ helicases use a molecular wedge element to seperate the double-stranded DNA", explains Prof. Kisker. "In RecQ4 we could not identify such a structure so far. That leads to the question, how the enzyme performs this strand separation mechanism?" Potentially, RecQ4 could strongly bend the DNA in order to weaken the paired bases and thereby separate the DNA strands - a mechanism known from bacterial RecQ helicases. An exceptional role for RecQ4 is also assumed based on its special cellular distribution: it is the only RecQ helicase, which localizes to mitochondria in addition to the cell nucleus and the cytoplasm. Thus, the enzyme might also be involved in replication and preservation of mitochondrial DNA.

Development of therapeutic approaches

Recently published in Nature Communications, the results on the RecQ4 helicase provide novel insights into the architecture and function of this important protein. Moreover, the structure of RecQ4 represents a valuable model to understand and investigate the development of RecQ4-associated diseases. Finally, due to the unique structure and the prominently elevated expression levels in cells of different cancer types, RecQ4 could resemble a promising target to develop novel therapeutic approaches in the fight against cancer.

Publication:
Kaiser S., Sauer F., Kisker C. (2017) The structural and functional characterization of human RecQ4 reveals insights into its helicase mechanism. Nature Communications 8, 15907

Website:
http://www.rudolf-virchow-zentrum.de/home.html
http://virchow.uni-wuerzburg.de/kiskerlab/

Contact:
Prof. Dr. Caroline Kisker (Structural Biology, Rudolf Virchow Center)
Tel. +49 (0)931 31 - 80405, caroline.kisker@virchow.uni-wuerzburg.de

Dr. Frank Sommerlandt (Public Science Center, Rudolf Virchow Center)
Tel. +49 (0)931 31 - 88449, frank.sommerlandt@uni-wuerzburg.de

Dr. Frank Sommerlandt | idw - Informationsdienst Wissenschaft

Further reports about: Biomedizin DNA RecQ double-stranded DNA enzyme enzymes genetic information helicase key enzyme

More articles from Life Sciences:

nachricht Barium ruthenate: A high-yield, easy-to-handle perovskite catalyst for the oxidation of sulfides
16.07.2018 | Tokyo Institute of Technology

nachricht The secret sulfate code that lets the bad Tau in
16.07.2018 | American Society for Biochemistry and Molecular Biology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Subaru Telescope helps pinpoint origin of ultra-high energy neutrino

16.07.2018 | Physics and Astronomy

Barium ruthenate: A high-yield, easy-to-handle perovskite catalyst for the oxidation of sulfides

16.07.2018 | Life Sciences

New research calculates capacity of North American forests to sequester carbon

16.07.2018 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>