Two RIKEN researchers have developed a switch to control the formation and separation of DNA duplexes that may have implications in many biological processes, such as gene regulation.
Formation of complexes of our genetic building blocks, the nucleic acids, underlies many biological events. Hybridization of the nucleic acids, through interactions known as base pairing, forms the intricate complexes responsible for the formation of DNA duplexes. The ability to control hybridization, and consequently whether biological events take place, is a very important goal for scientists.
Now, Shinzi Ogasawara and Mizuo Maeda at the RIKEN Advanced Science Institute, Wako, have developed a light-controlled switch that directs the formation and destabilization of a series of DNA duplexes (1).
They designed the photoswitch, a photochromic nucleoside (PCN), with several fundamental properties and benefits. The switch can be easily incorporated into a DNA strand and its physical conformation can be altered reversibly when irradiated by an external light source. Change of the physical conformation, by isomerization, disrupts and destabilizes the hybridization of two DNA strands. Another benefit of the PCN switch is that installing it into DNA has little influence on the structure of the duplex when it forms. Further, the PCN can be used as molecular trace label because it is fluorescent. This PCN photoswitch is therefore easy to track in the body and could be used in living cells without disruption.
The researchers irradiated a series of reaction mixtures containing PCN-modified DNA duplexes, which were fluorescent, with light at 370 nm for 5 minutes. After this time, only a slight fluorescence was seen. The PCN fragments had isomerized and the duplex broken. They then irradiated the mixtures at 254 nm for 2 minutes and the fluorescence returned, indicating a change back in conformation of the PCNs and importantly, hybridization to re-form the duplexes. This switching showed good reversibility over two cycles.
Surprisingly, this easy switching system also works below room temperature. Ogasawara is naturally pleased with the current results. “There were no particular problems we had to overcome,” he says. However, the synthesis of the PCNs was not as straightforward as they would have liked.
Ogasawara and Maeda now want to build on the results of this current study. “We plan to apply this technology to gene regulation such as antigene, antisense and siRNA,” says Ogasawara. “We think that this light-switching technique can be applied to nanotechnology, for example [using] light [to] control DNA nanomachines and architectures.”
1. Ogasawara, S. & Maeda, M. Straightforward and reversible photoregulation of hybridization by using a photochromic nucleoside. Angewandte Chemie International Edition 47, 8839–8842 (2008).
The corresponding author for this highlight is based at the RIKEN Bioengineering Laboratory
Mass spectrometry sheds new light on thallium poisoning cold case
14.12.2018 | University of Maryland
Protein involved in nematode stress response identified
14.12.2018 | University of Illinois College of Agricultural, Consumer and Environmental Sciences
The more objects we make "smart," from watches to entire buildings, the greater the need for these devices to store and retrieve massive amounts of data quickly without consuming too much power.
Millions of new memory cells could be part of a computer chip and provide that speed and energy savings, thanks to the discovery of a previously unobserved...
What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...
A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.
The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...
A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.
Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...
Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...
12.12.2018 | Event News
10.12.2018 | Event News
06.12.2018 | Event News
14.12.2018 | Power and Electrical Engineering
14.12.2018 | Physics and Astronomy
14.12.2018 | Physics and Astronomy