Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Hepatitis C Helicase Unwinds DNA In A Spring-Loaded, 3-Step Process

27.07.2007
The process by which genes are duplicated is mysterious and complex, involving a cast of characters with diverse talents and the ability to play well with others in extremely close quarters.

A key player on this stage is an enzyme called a helicase. Its job is to unwind the tightly coiled chain of nucleic acids the DNA or RNA molecule that spells out the organisms genetic code so that another enzyme, a polymerase, can faithfully copy each nucleotide in the code.

Researchers at the University of Illinois, Yale University and the Howard Hughes Medical Institute have shed new light on how the Hepatitis C helicase plays this role, using a technique developed at Illinois that can track how a single molecule of RNA or DNA unwinds. Their research findings appear tomorrow in the journal, Science.

Getting at the underlying mechanisms of replication is no easy task. Structural studies involve crystallizing the DNA-protein complexes to see how they interact. Biochemists look at the agents of a reaction, the energy used and how much time lapses between steps. Such studies measure the behavior of hundreds of thousands of molecules at a time, and the results describe a whole population of reactions.

Using single-molecule fluorescence analysis, the research team tracked how the hepatitis C helicase, NS3, unwound a duplexed DNA molecule tagged with a fluorescent label on each strand of its double-stranded region. (The NS3 helicase is primarily involved in unwinding the single-stranded RNA of the hepatitis virus, but it can also act on DNA. This suggests that the helicase plays a role in unwinding double-stranded host DNA during infection. The duplex created for the experiment included both single- and double-stranded DNA; fluorescent labels were located in the double-stranded region.)

By tracking the gradually increasing distance between the two marked nucleotides as the strands separated in an unwinding event, the researchers were able to measure the rate at which the unwinding occurred. What they found was that the DNA unwound in discrete jumps: Three nucleotide pairs (base pairs) had to be unhitched from one another before an unwinding event occurred.

Its like youre adding tension to a spring, said U. of I. physics professor Taekjip Ha, a researcher on the study and an affiliate of the Institute for Genomic Biology and the Howard Hughes Medical Institute. You are loading the spring with small mechanical movements until finally you have accumulated enough tension on the DNA-protein complex to cause the rapid unwinding of three base pairs.

Such reactions are energetically intensive, requiring the input of adenosine triphosphate (ATP) a cellular fuel source. The researchers observed that three ATP molecules were consumed in each unwinding reaction, indicating that three hidden steps, each involving the unhitching of one base pair, occurred for each unwinding event.

Although one molecule of ATP contains enough energy to unwind as many as 10 base pairs, the researchers said they were not surprised by the high-energy costs of the reaction.

Helicases work hand in hand with polymerases in replication, so it makes sense that the helicase would work on one base pair at a time, said Institute for Genomic Biology professor Sua Myong, who is lead author on the study. Its a very systematic,one-base-pair translocation that may help the polymerase accurately copy genes one base at a time.

The helicase must also navigate around a lot of obstacles: proteins and other co-factors that are involved in replication. This requires extra energy. Ha compared the energy needs of the NS3 helicase to those of a sport utility vehicle.

Its not fuel efficient but in principle it could also go off-road, carry some luggage or maneuver around barriers, he said. So it may actually make sense to develop a low-efficiency motor because then you have extra energy to do extra work when needed.

Myong noted that NS3 is the only helicase in the viral genome, and that it is already being targeted in pharmaceutical studies to combat Hepatitis C infection. It also belongs to the largest of four helicase superfamilies, so the new findings could have relevance across many organisms.

Funding for this research was provided by the National Institute of General Medical Sciences at the National Institutes of Health.

Diana Yates | University of Illinois
Further information:
http://www.uiuc.edu

Further reports about: Hepatitis NS3 double-stranded helicase pair reaction unwind unwinding

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>