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 Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH

nachricht Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

Helmholtz International Fellow Award for Sarah Amalia Teichmann

20.01.2017 | Awards Funding

An innovative high-performance material: biofibers made from green lacewing silk

20.01.2017 | Materials Sciences

Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery

20.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>