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Cryo-EM reveals insight into vital DNA repair process

New research, using cutting-edge cryo-electron microscopy (cryo-EM), has revealed key insights into a vital DNA repair process, which is implicated in resistance to cancer treatments.

Led by the University of Glasgow and published in Nature Structural Biology, the research 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 (pictured) – 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 removed from the damaged site – a process known as deubiquitination.

Now, 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.

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.

www.glasgow.ac.uk

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