Sheffield scientists capture snapshots of enzymes trimming branched DNA after cell division
Scientists have unlocked a crucial part of the mystery as to how our DNA can replicate and repair itself – something which is essential for all life forms.
The new research, conducted by leading scientists at the University of Sheffield, has revealed how branched DNA molecules are removed from the iconic double-helical structure –a process which scientists have been looking to unlock for over 20 years.
Jon Sayers, Professor of Functional Genomics at the University of Sheffield and lead author of the study, said, “Branched DNA features in several episodes of the X-Files as Agent Scully suspects aliens inserted it in her blood. In reality, far from being of alien origin, branched DNA is formed every day in our bodies. It happens every time our cells divide. These branches are essential intermediates formed during the process of copying our DNA.”
The interdisciplinary team from the University’s Departments of Infection, Immunity and Cardiovascular Disease, and Molecular Biology and Biotechnology, captured never-before-seen snapshots of the molecular events in incredible detail. They show how Flap EndoNuclease enzymes (FENs) trim branched DNA molecules after cells have divided.
The scientists found the FEN threads the free end of the branch through a hole in the enzyme before sliding along to the trunk where it acts like a pair of molecular secateurs, trimming the branch and restoring the iconic double-helix.
The team made the discovery using the Diamond Light Source – the UK’s synchrotron which works like a giant microscope harnessing the power of electrons to produce bright X-ray light which scientists can use to study anything from fossils and jet engines to viruses and vaccines.
Professor Sayers said, “The FENs analysed in the study are very similar to those used in diagnostic tests for genetic diseases, bacteria and viruses. Understanding how they work will help to engineer better and more reliable tests and tools for laboratory research and hospital diagnostics labs.
“Because DNA replication is essential for all life forms, understanding how it works at a molecular level provides insight into one of the most basic cellular processes common to all life.
“The enzymes that carry out this process are sometimes involved in cancer. They have been linked to tumour progression and mutation, so this discovery could pave the way for better diagnostics or new drugs.”
He added, “Knowing how these enzymes work could aid development of new antimicrobial drugs that may one day be used to fight antibiotic resistant bacteria.”
Results of the were published in Nature Structural & Molecular Biology.
Dr John Rafferty, from the University of Sheffield’s Department of Molecular Biology and Biotechnology and author on the study, said, “We can now see the details of how cells have evolved to tidy up after themselves as they copy their DNA, which reduces their risk of harmful mutations. This sort of information is fundamental in helping us understand and maybe treat those cells where occasionally things do go wrong.”