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.
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
More genes are active in high-performance maize
19.01.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn
How plants see light
19.01.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau
On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.
We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...
What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...
For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.
Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...
At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.
No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...
Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.
Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...
08.01.2018 | Event News
11.12.2017 | Event News
08.12.2017 | Event News
19.01.2018 | Materials Sciences
19.01.2018 | Health and Medicine
19.01.2018 | Physics and Astronomy