Cryo-EM reveals Key Insight into Vital DNA repair process
Scientists at the University of Glasgow have revealed key insights into a vital DNA repair process which is implicated in resistance to cancer treatments, using cryo-electron microscopy.
Led by the University of Glasgow the research [1] is based on data and models collected from the Scottish Centre for Macromolecular Imaging (SCMI) and was conducted with colleagues at the University of Dundee.
The study looks at a toxic type of DNA damage called inter-strand crosslinks, which is normally repaired through a process initiated by a single molecule of ubiquitin – a protein commonly found in humans, animals and plants – being attached to each of the affected strands of DNA. In order to complete the DNA repair process the ubiquitin molecule must also be successfully removed from the damaged site – a process known as deubiquitination.
Now, for the fi rst time, researchers are able to show at a molecular level, the exact snapshot in time when the ubiquitin molecule is about to be removed by the targeting enzyme USP1 (Ubiquitin carboxyl-terminal hydrolase). To do this scientists used the cutting-edge electron microscope at the SCMI and with the data are now able to understand how this complex process occurs.
Credit: University of Glasgow
Understanding how USP1 interacts with ubiquitin during the removal process is considered to be scientifi cally important and opens the door to further research in the area that could have impacts on cancer and other diseases. In cancer cells, effi cient functioning of USP1 can help repair any damage caused by drug therapies, thereby making treatment of the disease less successful. As a result, USP1 has been identifi ed as a potential drug target for overcoming cancer resistance to treatment.
Professor Helen Walden, lead author of the study and professor of structural biology at the University of Glasgow, said: “The developments in cryo-EM over recent years have revolutionised structural biology, and we are really excited to capture this important complex, and how this will allow us to understand the DNA repair on a deep molecular level.”
The new £5 million SCMI is hosted by the University of Glasgow and is part of the Medical Research Council-University of Glasgow Centre for Virus Research (CVR) and is the result of collaboration between researchers from Glasgow, Edinburgh, Dundee and St Andrews. As a structural biology centre, it is home to a cutting-edge electron microscope – the fi rst of its kind in Scotland – which will be used to image biological molecules at the atomic level.
The work is funded by the European Research Council and the Medical Research Council (MRC). 1. Published in Nature Structural Biology. More information online:
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Structural Kinks Create Smart Components
Physicists at the University of Sussex have discovered that the tiniest microchips yet can be made from graphene and other 2D-materials. By creating kinks in the structure of graphene, the researchers made the nanomaterial behave like a transistor and have shown that when a strip of graphene is crinkled in this way, it can behave like a microchip, being around 100 times smaller than conventional microchips.
Professor Alan Dalton in the School of Mathematical and Physical Sciences at the University of Sussex, said: “We’re mechanically creating kinks in a layer of graphene. It’s a bit like nano-origami.
“Using these nanomaterials will make our computer chips smaller and faster. It is absolutely critical that this happens as computer manufacturers are now at the limit of what they can do with traditional semiconducting technology. Ultimately, this will make our computers and phones thousands of times faster in the future.
“This kind of technology; ‘straintronics’ using nanomaterials as opposed to electronics – allows space for more chips inside any device. Everything we want to do with computers – to speed them up – can be done by crinkling graphene like this.”
Dr Manoj Tripathi, Research Fellow in Nano-structured Materials at the University of Sussex and lead author on the paper, said: “Instead of having to add foreign materials into a device, we’ve shown we can create structures from graphene and other 2D materials simply by adding deliberate kinks into the structure. By making this sort of corrugation we can create a smart electronic component, like a transistor, or a logic gate.”
The development is a greener, more sustainable technology. Because no additional materials need to be added and because this process works at room temperature rather than high temperature, it uses less energy to create.
The research was published in the ACS Nano journal. More information online:
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