The breakthrough described in an article in the Nov. 17 issue of the journal Science reveals important structural information about the gyrations of DNA during transcription and the effects of those gyrations on the process.
The discoveries, which inform our understanding of the structure and mechanics of RNAP -- an enzyme responsible for making RNA from a DNA or RNA template -- can help set the stage for new opportunities in combating bacterial diseases that kill 13 million people worldwide each year.
The researchers used single-molecule spectroscopy to monitor the transfer of energy between -- and hence the distance separating -- pairs of fluorescent chemical tags attached to key structural elements of RNAP and the DNA double helix during initiation of the transcription process.
The changes in the distances between these tags confirmed that transcription proceeds initially through a "scrunching" mechanism in which, much like a fisherman reeling in a catch, RNAP remains in a fixed position while it pulls the flexible DNA strand of the gene within itself and past the enzyme's reactive center to form the RNA product.
These changes are inconsistent with other theories that had suggested that RNAP moves along the DNA strand as a complete block in a process resembling the movement of an inchworm.
The research team is comprised of Achillefs N. Kapanidis, Emmanuel Margeat, Sam On Ho, Ekaterine Kortkhonjia and Shimon Weiss of the UCLA Department of Chemistry and Biochemistry, the Department of Physiology and the California NanoSystems Institute (CNSI). The team collaborated with Richard H. Ebright, Howard Hughes Medical Institute, Waksman Institute and Department of Chemistry, Rutgers University.
The scrunching model implies that the scrunched DNA is expelled from the enzyme channel at predictable sites that are available for interaction with transcription regulatory proteins. Beyond resolving the mechanism for initiation, the significance of this work is in pointing out an important regulation "checkpoint." Scrunched DNA is likely to play a major role in future studies of transcription regulation, and possibly become a focus for antibiotic drug discovery efforts.
"These are issues that we were not able to resolve until the development of the single molecule methods that we employed in these studies," Ebright said. "These methods involve detecting and manipulating single molecules, one at a time -- a breakthrough in its own right."
"The study of molecular machines, the dynamics of their moving parts and their translocation on molecular tracks is of great interest to nanotechnologists at the CNSI," said Weiss, the leader of the UCLA team. "Beyond furthering the understanding of transcription regulation, the novel methods and findings of this work will aid future studies of other molecular machines involved in cell replication, transcription and protein synthesis."
Jennifer Marcus | EurekAlert!
Nerves control the body’s bacterial community
26.09.2017 | Christian-Albrechts-Universität zu Kiel
Ageless ears? Elderly barn owls do not become hard of hearing
26.09.2017 | Carl von Ossietzky-Universität Oldenburg
Controlling electronic current is essential to modern electronics, as data and signals are transferred by streams of electrons which are controlled at high speed. Demands on transmission speeds are also increasing as technology develops. Scientists from the Chair of Laser Physics and the Chair of Applied Physics at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) have succeeded in switching on a current with a desired direction in graphene using a single laser pulse within a femtosecond ¬¬ – a femtosecond corresponds to the millionth part of a billionth of a second. This is more than a thousand times faster compared to the most efficient transistors today.
Graphene is up to the job
At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.
Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
26.09.2017 | Life Sciences
26.09.2017 | Physics and Astronomy
26.09.2017 | Information Technology